Structural biology

  • Article | | open

    SecB homologs can be associated with stress-responsive type II toxin–antitoxin (TA) systems and form tripartite toxin-antitoxin-chaperone systems (TAC). Here the authors provide structural insights into TACs by presenting the crystal structure of the M. tuberculosis TA-associated SecB chaperone in complex with the C-terminal ChAD (chaperone addiction) extension of the antitoxin HigA1.

    • Valérie Guillet
    • , Patricia Bordes
    • , Cécile Bon
    • , Julien Marcoux
    • , Virginie Gervais
    • , Ambre Julie Sala
    • , Suzana Dos Reis
    • , Nawel Slama
    • , Israel Mares-Mejía
    • , Anne-Marie Cirinesi
    • , Laurent Maveyraud
    • , Pierre Genevaux
    •  & Lionel Mourey
  • Article | | open

    Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.

    • M. Teresa Bertran
    • , Stéphane Mouilleron
    • , Yanxiang Zhou
    • , Rakhi Bajaj
    • , Federico Uliana
    • , Ganesan Senthil Kumar
    • , Audrey van Drogen
    • , Rebecca Lee
    • , Jennifer J. Banerjee
    • , Simon Hauri
    • , Nicola O’Reilly
    • , Matthias Gstaiger
    • , Rebecca Page
    • , Wolfgang Peti
    •  & Nicolas Tapon
  • Article | | open

    The fusion peptide (FP) of HIV envelope (Env) is critical in the cell entry process. Here, Kumar et al. present crystal structures of B41 SOSIP.664 Env trimer and show the dynamic nature of the FP and proximal region, which likely relates to conformational rearrangements required for membrane fusion.

    • Sonu Kumar
    • , Anita Sarkar
    • , Pavel Pugach
    • , Rogier W. Sanders
    • , John P. Moore
    • , Andrew B. Ward
    •  & Ian A. Wilson
  • Article | | open

    Adenovirus based (AdV) vectors are promising platforms for therapeutics and vaccines, but receptor usage of serotypes in clinical development remains unclear. Here, based on crystal structures and modeling, Baker et al. show that HAdV-D26/48 fiber knob protein interacts weakly with CAR but not with CD46 or DSG2.

    • Alexander T. Baker
    • , Alexander Greenshields-Watson
    • , Lynda Coughlan
    • , James A. Davies
    • , Hanni Uusi-Kerttula
    • , David K. Cole
    • , Pierre J. Rizkallah
    •  & Alan L. Parker
  • Article | | open

    Quaternary contacts mediated by an extended heavy-chain framework region 3 (FR3) have been shown to improve binding to HIV envelope and virus neutralization for a few antibodies. Here, Liu et al. engraft such an FR3 loop onto several potent broadly neutralizing antibodies, resulting in improved neutralization activity and pharmacokinetics.

    • Qingbo Liu
    • , Yen-Ting Lai
    • , Peng Zhang
    • , Mark K. Louder
    • , Amarendra Pegu
    • , Reda Rawi
    • , Mangaiarkarasi Asokan
    • , Xuejun Chen
    • , Chen-Hsiang Shen
    • , Gwo-Yu Chuang
    • , Eun Sung Yang
    • , Huiyi Miao
    • , Yuge Wang
    • , Anthony S. Fauci
    • , Peter D. Kwong
    • , John R. Mascola
    •  & Paolo Lusso
  • Article | | open

    No structural data have been available for RNA polymerase holoenzymes or transcription initiation complexes that contain extracytoplasmic σ factors. Here the authors report the crystal structures of transcription initiation complexes comprising Mycobacterium tuberculosis RNA polymerase, extracytoplasmic σ factor σL and promoter DNA.

    • Wei Lin
    • , Sukhendu Mandal
    • , David Degen
    • , Min Sung Cho
    • , Yu Feng
    • , Kalyan Das
    •  & Richard H. Ebright
  • Article | | open

    The antitermination factor RfaH adopts two functional states where its C-terminal domain is folded either as an α-helical hairpin or β-barrel. Here the authors employ solution state NMR measurements to show that the C-terminal domain transforms into the β-barrel only upon binding to the elongation complex and refolds back after dissociation.

    • Philipp Konrad Zuber
    • , Kristian Schweimer
    • , Paul Rösch
    • , Irina Artsimovitch
    •  & Stefan H. Knauer
  • Article | | open

    Many 2-Cystein Peroxiredoxins (Prx) can either function as peroxidases or chaperones when exposed to stress. Here the authors present the structures of Leishmania infantum mitochondrial Prx alone and with a bound model client protein, use crosslinking to reveal interaction regions that stabilize the bound client, and provide insights into the mechanism by which Prx’s adopt chaperone activity.

    • Filipa Teixeira
    • , Eric Tse
    • , Helena Castro
    • , Karl A. T. Makepeace
    • , Ben A. Meinen
    • , Christoph H. Borchers
    • , Leslie B. Poole
    • , James C. Bardwell
    • , Ana M. Tomás
    • , Daniel R. Southworth
    •  & Ursula Jakob
  • Article | | open

    Many Gram-negative bacteria rely on a type III secretion system (T3SS) for their pathogenicity. Here authors present the cryo-EM structure of the E.coli T3SS ATPase-central stalk complex, which forms a homohexameric, asymmetric pore with different functional states.

    • Dorothy D. Majewski
    • , Liam J. Worrall
    • , Chuan Hong
    • , Claire E. Atkinson
    • , Marija Vuckovic
    • , Nobuhiko Watanabe
    • , Zhiheng Yu
    •  & Natalie C. J. Strynadka
  • Article | | open

    Elp3 is the catalytic subunit of the eukaryotic Elongator complex that catalyzes posttranscriptional tRNA modifications. Here the authors present the crystal structures of an acetyl-CoA analog bound bacterial Elp3 and a monomeric archaeal Elp3 and show that Elp3 functions as a tRNA modification enzyme in all domains of life.

    • Ting-Yu Lin
    • , Nour El Hana Abbassi
    • , Karol Zakrzewski
    • , Andrzej Chramiec-Głąbik
    • , Małgorzata Jemioła-Rzemińska
    • , Jan Różycki
    •  & Sebastian Glatt
  • Article | | open

    The FDA approved drug aprepitant is an antagonist of the Neurokinin 1 receptor (NK1R). Here the authors present aprepitant bound NK1R crystal structures and use NMR spectroscopy to gain further insights into the dynamics of aprepitant binding, which is of interest for further drug development.

    • Shuanghong Chen
    • , Mengjie Lu
    • , Dongsheng Liu
    • , Lingyun Yang
    • , Cuiying Yi
    • , Limin Ma
    • , Hui Zhang
    • , Qing Liu
    • , Thomas M. Frimurer
    • , Ming-Wei Wang
    • , Thue W. Schwartz
    • , Raymond C. Stevens
    • , Beili Wu
    • , Kurt Wüthrich
    •  & Qiang Zhao
  • Article | | open

    Zinc ions (Zn2+) are imported by Golgi-resident transporters but the function of zinc in the early secretory pathway has remained unknown. Here the authors find that Zn2+ regulates protein quality control in the early secretory pathway by demonstrating that the pH-sensitive chaperone ERp44 binds Zn2+ and solving the Zn2+-bound ERp44 structure.

    • Satoshi Watanabe
    • , Yuta Amagai
    • , Sara Sannino
    • , Tiziana Tempio
    • , Tiziana Anelli
    • , Manami Harayama
    • , Shoji Masui
    • , Ilaria Sorrentino
    • , Momo Yamada
    • , Roberto Sitia
    •  & Kenji Inaba
  • Article | | open

    Kinetochore function depends on H4K20 monomethylation in centromeric nucleosomes but the underlying mechanism is unclear. Here, the authors provide evidence that the centromere-specific nucleosome subunit CENP-A facilitates H4K20 methylation by enabling a conformational change of the H4 N-terminal tail.

    • Yasuhiro Arimura
    • , Hiroaki Tachiwana
    • , Hiroki Takagi
    • , Tetsuya Hori
    • , Hiroshi Kimura
    • , Tatsuo Fukagawa
    •  & Hitoshi Kurumizaka
  • Article | | open

    The TERB1-TERB2-MAJIN complex mediates the attachment of telomeres to the nuclear envelope. Here the authors present the crystal structures of the human TERB1-TERB2 and TERB2-MAJIN subcomplexes and show that Terb2 mutations, which abolish complex formation cause aberrant homologous pairing and disordered synapsis in mouse.

    • Yan Wang
    • , Yanyan Chen
    • , Juan Chen
    • , Lijun Wang
    • , Leitong Nie
    • , Juanjuan Long
    • , Haishuang Chang
    • , Jian Wu
    • , Chenhui Huang
    •  & Ming Lei
  • Article | | open

    The role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in maintenance of protein folding homeostasis inside the ER has remained unclear. Here the authors determine the structure of the complex between MANF and the ER-localized chaperone BiP and provide evidence that MANF serves as an anti-nucleotide exchange factor for BiP.

    • Yahui Yan
    • , Claudia Rato
    • , Lukas Rohland
    • , Steffen Preissler
    •  & David Ron
  • Article | | open

    Rix7 is a type II AAA-ATPase that is required for the assembly of the large ribosomal subunit. Here the authors present the 4.5 Å cryo-EM structure of the Rix7 homohexamer with a polypeptide fragment bound in its central channel and provide insights into the function of Rix7 as a molecular unfoldase.

    • Yu-Hua Lo
    • , Mack Sobhany
    • , Allen L. Hsu
    • , Brittany L. Ford
    • , Juno M. Krahn
    • , Mario J. Borgnia
    •  & Robin E. Stanley
  • Article | | open

    PGAM5 is a mitochondrial protein phosphatase whose functions include regulation of mitophagy and cell death. Here, the authors use x-ray crystallography and EM to show that PGAM5 forms dodecameric rings and filaments in solution, and find that PGAM5 rings are essential for catalysis and for a structural effect PGAM5 has on mitochondrial membranes, independently of catalytic activity.

    • Karen Ruiz
    • , Tarjani M. Thaker
    • , Christopher Agnew
    • , Lakshmi Miller-Vedam
    • , Raphael Trenker
    • , Clara Herrera
    • , Maria Ingaramo
    • , Daniel Toso
    • , Adam Frost
    •  & Natalia Jura
  • Article | | open

    IRSp53 is a key regulator of filopodia formation and cell migration. Here, the authors elucidate a mechanism of phosphorylation-dependent inhibition of IRSp53 by 14-3-3, which impedes the interactions of IRSp53 with membranes and downstream cytoskeletal effectors.

    • David J. Kast
    •  & Roberto Dominguez
  • Article | | open

    Designing interfaces that can induce protein-protein interactions is a challenging problem. Here the authors show that a five amino acid sequence known to mediate domain swapping in cystatins can drive oligomerization when grafted onto functionally and structurally unrelated host proteins, providing a simple approach to the design of protein assemblies.

    • Neha Nandwani
    • , Parag Surana
    • , Hitendra Negi
    • , Nahren M. Mascarenhas
    • , Jayant B. Udgaonkar
    • , Ranabir Das
    •  & Shachi Gosavi
  • Article | | open

    The chaperone Hsp90 is a potential target for the development of drugs against fungal pathogens. Here the authors determine the structure of the Hsp90 nucleotide-binding domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.

    • Luke Whitesell
    • , Nicole Robbins
    • , David S. Huang
    • , Catherine A. McLellan
    • , Tanvi Shekhar-Guturja
    • , Emmanuelle V. LeBlanc
    • , Catherine S. Nation
    • , Raymond Hui
    • , Ashley Hutchinson
    • , Cathy Collins
    • , Sharanya Chatterjee
    • , Richard Trilles
    • , Jinglin L. Xie
    • , Damian J. Krysan
    • , Susan Lindquist
    • , John A. Porco Jr.
    • , Utpal Tatu
    • , Lauren E. Brown
    • , Juan Pizarro
    •  & Leah E. Cowen
  • Article | | open

    Plants are dependent on controlled sugar uptake via Monosaccharide Transporters, such as STP10, for correct organ development, sugar accumulation in fruits and microbial defense. Here authors present the crystal structure of STP10 bound to glucose which sheds light on the fundamental principles of sugar transport in the plant-unique MST superfamily.

    • Peter Aasted Paulsen
    • , Tânia F. Custódio
    •  & Bjørn Panyella Pedersen
  • Article | | open

    Septins are cytoskeletal filaments that localize at constriction sites and impact membrane remodeling. Here authors examine the curvature sensitivity of septins using bilayers on wavy patterns and derive a theoretical model that quantitatively describe the results.

    • Alexandre Beber
    • , Cyntia Taveneau
    • , Manuela Nania
    • , Feng-Ching Tsai
    • , Aurelie Di Cicco
    • , Patricia Bassereau
    • , Daniel Lévy
    • , João T. Cabral
    • , Hervé Isambert
    • , Stéphanie Mangenot
    •  & Aurélie Bertin
  • Article | | open

    Nucleocytoplasmic large DNA viruses are a group of viruses that infect many eukaryotic hosts. Here, the authors provide a 3.5 Å resolution icosahedrally-averaged capsid structure of Paramecium bursaria chlorella virus 1 and show how 1800 minor capsid proteins form a hexagonal network below the outer capsid shell.

    • Qianglin Fang
    • , Dongjie Zhu
    • , Irina Agarkova
    • , Jagat Adhikari
    • , Thomas Klose
    • , Yue Liu
    • , Zhenguo Chen
    • , Yingyuan Sun
    • , Michael L. Gross
    • , James L. Van Etten
    • , Xinzheng Zhang
    •  & Michael G. Rossmann
  • Article | | open

    There is increasing effort to improve the signal sensitivity and explore the hyperpolarization dynamics. Here the authors demonstrate the parahydrogen spin transfer dynamics in compounds containing 15N using SABRE hyperpolarization technique with different strengths of the magnetic field.

    • Jacob R. Lindale
    • , Shannon L. Eriksson
    • , Christian P. N. Tanner
    • , Zijian Zhou
    • , Johannes F. P. Colell
    • , Guannan Zhang
    • , Junu Bae
    • , Eduard Y. Chekmenev
    • , Thomas Theis
    •  & Warren S. Warren
  • Article | | open

    The DNA ligase of African swine fever virus is one of the most error-prone ligases identified to date, but underlying molecular details are lacking. Here, Chen et al. report four AsfvLIG:DNA structures and identify a unique N-terminal domain and four unique active site residues that are crucial for its catalytic efficiency.

    • Yiqing Chen
    • , Hehua Liu
    • , Chun Yang
    • , Yanqing Gao
    • , Xiang Yu
    • , Xi Chen
    • , Ruixue Cui
    • , Lina Zheng
    • , Suhua Li
    • , Xuhang Li
    • , Jinbiao Ma
    • , Zhen Huang
    • , Jixi Li
    •  & Jianhua Gan
  • Article | | open

    Enhanced Wnt receptor activity is a major cause of cancer development. Here the authors identify camelid single-domain antibody fragments (VHHs) that bind to the Wnt receptor LRP5/6 ectodomain, determine the crystal structures and show that these VHHs selectively inhibit Wnt3- mediated cellular responses and block the growth of mutant Wnt-hypersensitive intestinal tumor organoids.

    • Nicola Fenderico
    • , Revina C. van Scherpenzeel
    • , Michael Goldflam
    • , Davide Proverbio
    • , Ingrid Jordens
    • , Tomica Kralj
    • , Sarah Stryeck
    • , Tarek Z. Bass
    • , Guy Hermans
    • , Christopher Ullman
    • , Teodor Aastrup
    • , Piet Gros
    •  & Madelon M. Maurice
  • Article | | open

    The architecture of functional TNTs is still under debate. Here, the authors combine correlative FIB-SEM, light- and cryo-electron microscopy approaches to elucidate the structure of TNTs in neuronal cells, showing that they form structures that are distinct form other membrane protrusions.

    • Anna Sartori-Rupp
    • , Diégo Cordero Cervantes
    • , Anna Pepe
    • , Karine Gousset
    • , Elise Delage
    • , Simon Corroyer-Dulmont
    • , Christine Schmitt
    • , Jacomina Krijnse-Locker
    •  & Chiara Zurzolo
  • Article | | open

    The interactions of lignin with polysaccharides in plant secondary cell walls are not well understood. Here the authors employ solid-state NMR measurements to analyse intact stems of maize, Arabidopsis, switchgrass and rice and observe that lignin self-aggregates and forms highly hydrophobic microdomains that make extensive surface contacts to xylan.

    • Xue Kang
    • , Alex Kirui
    • , Malitha C. Dickwella Widanage
    • , Frederic Mentink-Vigier
    • , Daniel J. Cosgrove
    •  & Tuo Wang
  • Article | | open

    Context-dependent inhibition of NMDA receptors has important therapeutic implications for treatment of neurological diseases. Here, the authors use structural biology and biophysics to describe the basis for pH-dependent inhibition for a class of allosteric NMDAR inhibitors, called the 93-series.

    • Michael C. Regan
    • , Zongjian Zhu
    • , Hongjie Yuan
    • , Scott J. Myers
    • , Dave S. Menaldino
    • , Yesim A. Tahirovic
    • , Dennis C. Liotta
    • , Stephen F. Traynelis
    •  & Hiro Furukawa
  • Article | | open

    In fission yeast, Erh1, ortholog of human ERH, interacts with the YTH family RNA binding protein Mmi1 to form the Erh1-Mmi1 complex (EMC), which has been implicated in gene silencing. Here, the authors present the cocrystal structure of Erh1 homodimers interacting with Mmi1 and further characterise the role of EMC in facultative heterochromatin assembly and gene silencing.

    • Guodong Xie
    • , Tommy V. Vo
    • , Gobi Thillainadesan
    • , Sahana Holla
    • , Beibei Zhang
    • , Yiyang Jiang
    • , Mengqi Lv
    • , Zheng Xu
    • , Chongyuan Wang
    • , Vanivilasini Balachandran
    • , Yunyu Shi
    • , Fudong Li
    •  & Shiv I. S. Grewal
  • Article | | open

    Deubiquitinating enzymes (DUBs) are critical regulators of cellular processes by removing ubiquitin from specific targets. Here global kinetic modelling reveals the mechanism by which the low intrinsic activity of USP7 is substantially enhanced on a specific physiological target.

    • Robbert Q. Kim
    • , Paul P. Geurink
    • , Monique P. C. Mulder
    • , Alexander Fish
    • , Reggy Ekkebus
    • , Farid El Oualid
    • , Willem J. van Dijk
    • , Duco van Dalen
    • , Huib Ovaa
    • , Hugo van Ingen
    •  & Titia K. Sixma
  • Article | | open

    Activation of the PPARγ/RXRα pathway in luminal bladder cancers has mainly been linked to PPARG gene amplifications and activating point mutations in RXRα. Here, the authors identify recurrent PPARγ mutations with similar effects and elucidate the structural basis for this mutational PPARγ activation.

    • Natacha Rochel
    • , Clémentine Krucker
    • , Laure Coutos-Thévenot
    • , Judit Osz
    • , Ruiyun Zhang
    • , Elodie Guyon
    • , Wayne Zita
    • , Séverin Vanthong
    • , Oscar Alba Hernandez
    • , Maxime Bourguet
    • , Kays Al Badawy
    • , Florent Dufour
    • , Carole Peluso-Iltis
    • , Syrine Heckler-Beji
    • , Annick Dejaegere
    • , Aurélie Kamoun
    • , Aurélien de Reyniès
    • , Yann Neuzillet
    • , Sandra Rebouissou
    • , Claire Béraud
    • , Hervé Lang
    • , Thierry Massfelder
    • , Yves Allory
    • , Sarah Cianférani
    • , Roland H. Stote
    • , François Radvanyi
    •  & Isabelle Bernard-Pierrot
  • Article | | open

    GpsB is a cytosolic protein that modulates bacterial cell wall synthesis by interacting with cytoplasmic domains of peptidoglycan synthases. Here, Cleverley et al. describe structural features that are important for these interactions, and identify new interacting partners of GpsB in three bacterial species.

    • Robert M. Cleverley
    • , Zoe J. Rutter
    • , Jeanine Rismondo
    • , Federico Corona
    • , Ho-Ching Tiffany Tsui
    • , Fuad A. Alatawi
    • , Richard A. Daniel
    • , Sven Halbedel
    • , Orietta Massidda
    • , Malcolm E. Winkler
    •  & Richard J. Lewis
  • Article | | open

    Transient oligomeric species of the amyloid-β peptide (Aβ42) have been identified as key pathogenic agents in Alzheimer’s disease. Here the authors find that the aminosterol trodusquemine enhances Aβ42 aggregation and suppresses Aβ42-induced toxicity by displacing oligomers from cell membranes.

    • Ryan Limbocker
    • , Sean Chia
    • , Francesco S. Ruggeri
    • , Michele Perni
    • , Roberta Cascella
    • , Gabriella T. Heller
    • , Georg Meisl
    • , Benedetta Mannini
    • , Johnny Habchi
    • , Thomas C. T. Michaels
    • , Pavan K. Challa
    • , Minkoo Ahn
    • , Samuel T. Casford
    • , Nilumi Fernando
    • , Catherine K. Xu
    • , Nina D. Kloss
    • , Samuel I. A. Cohen
    • , Janet R. Kumita
    • , Cristina Cecchi
    • , Michael Zasloff
    • , Sara Linse
    • , Tuomas P. J. Knowles
    • , Fabrizio Chiti
    • , Michele Vendruscolo
    •  & Christopher M. Dobson
  • Article | | open

    Deregulation of the RAS GTPase cycle due to mutations in RAS genes is commonly associated with cancer development. Here authors use NMR and mass spectrometry to shows that KRAS phosphorylation via Src alters the conformation of switch I and II regions and thereby impacts the GTPase cycle.

    • Yoshihito Kano
    • , Teklab Gebregiworgis
    • , Christopher B. Marshall
    • , Nikolina Radulovich
    • , Betty P. K. Poon
    • , Jonathan St-Germain
    • , Jonathan D. Cook
    • , Ivette Valencia-Sama
    • , Benjamin M. M. Grant
    • , Silvia Gabriela Herrera
    • , Jinmin Miao
    • , Brian Raught
    • , Meredith S. Irwin
    • , Jeffrey E. Lee
    • , Jen Jen Yeh
    • , Zhong-Yin Zhang
    • , Ming-Sound Tsao
    • , Mitsuhiko Ikura
    •  & Michael Ohh
  • Article | | open

    Protein structure determination in complex biological samples is still challenging. Here, the authors develop a computational modeling-guided cross-linking mass spectrometry method, obtaining a high-resolution model of a 1.8 MDa protein assembly from cross-links detected in a mixture of human plasma and bacteria.

    • Simon Hauri
    • , Hamed Khakzad
    • , Lotta Happonen
    • , Johan Teleman
    • , Johan Malmström
    •  & Lars Malmström
  • Article | | open

    Tetrathiomolybdate (TM) and Cu-ATPases, e.g. Wilson (WLN) protein, affect the efficacy of common anticancer drug cisplatin. Here, the authors show that TM generates a protein dimer with a WLN domain by expelling copper and provide insight into the synergy of TM and cisplatin in cancer chemotherapy.

    • Tiantian Fang
    • , Wanbiao Chen
    • , Yaping Sheng
    • , Siming Yuan
    • , Qiaowei Tang
    • , Gongyu Li
    • , Guangming Huang
    • , Jihu Su
    • , Xuan Zhang
    • , Jianye Zang
    •  & Yangzhong Liu
  • Article | | open

    Spontaneous activity shifts at constant experimental conditions are widespread among ion channels but the molecular origins are poorly understood. Here, using solid-state NMR and MD simulations, the authors reveal that modal gating shifts in K + channels are caused by large shifts in the channel dynamics which perturb the selectivity filter.

    • Shehrazade Jekhmane
    • , João Medeiros-Silva
    • , Jing Li
    • , Felix Kümmerer
    • , Christoph Müller-Hermes
    • , Marc Baldus
    • , Benoît Roux
    •  & Markus Weingarth
  • Article | | open

    Squalene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and is a target for hypercholesteremia and cancer drug development. Here the authors present the crystal structures of the human SQLE catalytic domain alone and bound with small molecule inhibitors, which will facilitate the development of next-generation SQLE inhibitors.

    • Anil K. Padyana
    • , Stefan Gross
    • , Lei Jin
    • , Giovanni Cianchetta
    • , Rohini Narayanaswamy
    • , Feng Wang
    • , Rui Wang
    • , Cheng Fang
    • , Xiaobing Lv
    • , Scott A. Biller
    • , Lenny Dang
    • , Christopher E. Mahoney
    • , Nelamangala Nagaraja
    • , David Pirman
    • , Zhihua Sui
    • , Janeta Popovici-Muller
    •  & Gromoslaw A. Smolen
  • Article | | open

    Synaptic exocytosis depends on formation of the SNARE complex but its assembly mechanism is still under debate. Here, the authors identify an interaction between Munc13-1 and synaptobrevin-2 that is critical for the transition of the Munc18-1/syntaxin-1 complex to the SNARE complex.

    • Shen Wang
    • , Yun Li
    • , Jihong Gong
    • , Sheng Ye
    • , Xiaofei Yang
    • , Rongguang Zhang
    •  & Cong Ma
  • Article | | open

    P-glycoprotein, an ATP-binding cassette (ABC) transporter, extrudes a large variety of xenobiotics from the cell which protects tissues from toxins. Here authors solve a pair of X-ray structures of homodimeric P-glycoprotein and resolve structural elements proposed to participate in the mechanism of the transporter.

    • Atsushi Kodan
    • , Tomohiro Yamaguchi
    • , Toru Nakatsu
    • , Keita Matsuoka
    • , Yasuhisa Kimura
    • , Kazumitsu Ueda
    •  & Hiroaki Kato
  • Article | | open

    CD1 proteins present lipid antigens to T cells via the T cell receptor. Here the authors describe T cell reactivity to human membrane lipid moieties and provide structural data to define a molecular mechanism of promiscuous recognition of self-derived phospholipids.

    • Adam Shahine
    • , Peter Reinink
    • , Josephine F. Reijneveld
    • , Stephanie Gras
    • , Mira Holzheimer
    • , Tan-Yun Cheng
    • , Adriaan J. Minnaard
    • , John D. Altman
    • , Steffi Lenz
    • , Jacques Prandi
    • , Joanna Kubler-Kielb
    • , D. Branch Moody
    • , Jamie Rossjohn
    •  & Ildiko Van Rhijn
  • Article | | open

    Temsavir, a compound that inhibits HIV entry by binding envelope (Env), is currently in clinical development. Here, Lai et al. identify a more than 10-fold improved compound and, using lattice engineering, obtain crystal structures that give insights into improved inhibition between small molecules and Env.

    • Yen-Ting Lai
    • , Tao Wang
    • , Sijy O’Dell
    • , Mark K. Louder
    • , Arne Schön
    • , Crystal S. F. Cheung
    • , Gwo-Yu Chuang
    • , Aliaksandr Druz
    • , Bob Lin
    • , Krisha McKee
    • , Dongjun Peng
    • , Yongping Yang
    • , Baoshan Zhang
    • , Alon Herschhorn
    • , Joseph Sodroski
    • , Robert T. Bailer
    • , Nicole A. Doria-Rose
    • , John R. Mascola
    • , David R. Langley
    •  & Peter D. Kwong
  • Article | | open

    MLL3 and MLL4 are members of the SET1/MLL family of histone H3K4 methyltransferases, which are responsible for monomethylating histone H3K4 on enhancers. Here the authors show that an extended PHD domain (ePHD6) in MLL3 and MLL4 specifically recognizes an H4H18-containing fragment of histone H4, and that modifications of residues surrounding H4H18 modulate H4 binding to MLL3/4.

    • Yanli Liu
    • , Su Qin
    • , Tsai-Yu Chen
    • , Ming Lei
    • , Shilpa S. Dhar
    • , Jolene Caifeng Ho
    • , Aiping Dong
    • , Peter Loppnau
    • , Yanjun Li
    • , Min Gyu Lee
    •  & Jinrong Min
  • Article | | open

    Neurokinin receptors are G protein-coupled receptors. Here the authors present three crystal structures of the neurokinin 1 receptor (NK1R) in complex with small-molecule antagonists including aprepitant and netupitant and observe that these clinically approved compounds induce a conformational change in the receptor.

    • Jendrik Schöppe
    • , Janosch Ehrenmann
    • , Christoph Klenk
    • , Prakash Rucktooa
    • , Marco Schütz
    • , Andrew S. Doré
    •  & Andreas Plückthun
  • Article | | open

    DnaB helicases are motor proteins that couple ATP-hydrolysis to the movement of the protein along single-stranded DNA leading to a separation of double-stranded DNA at the replication fork. Here authors use solid-state NMR spectroscopy and reveal DnaB’s conformational responses to ATP hydrolysis and the resulting DNA loading and translocation.

    • Thomas Wiegand
    • , Riccardo Cadalbert
    • , Denis Lacabanne
    • , Joanna Timmins
    • , Laurent Terradot
    • , Anja Böckmann
    •  & Beat H. Meier
  • Article | | open

    Brain-specific angiogenesis inhibitor (BAI) is an adhesion G protein-coupled receptor that acts through the ELMO/DOCK/Rac signaling pathway. Here the authors provide molecular insights into BAI/ELMO interactions by solving the crystal structure of the C-terminal cytoplasmic tail of BAI bound to the RAE tandem domains of ELMO2.

    • Zhuangfeng Weng
    • , Chenghao Situ
    • , Lin Lin
    • , Zhenguo Wu
    • , Jinwei Zhu
    •  & Rongguang Zhang
  • Article | | open

    Eukaryotic transcription requires passage of RNA polymerase II (Pol II) through chromatin, which is impaired by nucleosomes. Here the authors report the cryo-EM structure of transcribing Pol II engaged with a downstream nucleosome core particle at an overall resolution of 4.4 Å, providing insights into the mechanism of chromatin transcription.

    • Lucas Farnung
    • , Seychelle M. Vos
    •  & Patrick Cramer