Proteins articles within Nature Communications

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  • Article
    | Open Access

    Understanding the dynamics of enzyme-substrate complexation provides an insight into potential drugs, but intermediate states are difficult to observe experimentally. Here, the authors use simulations and machine learning to analyse the binding of transition state inhibitors to purine nucleoside phosphorylase.

    • Sergio Decherchi
    • , Anna Berteotti
    •  & Andrea Cavalli

  • Article |

    Whether heterochromatin affects the physical properties of the nucleus is not known. Here, Furusawa et al. show that chromatin decompaction decreases the sturdiness of the nucleus in cultured cells and leads to lamina disruption and cardiac abnormalities in adult mice, suggesting a structural, non-genetic function for heterochromatin.

    • Takashi Furusawa
    • , Mark Rochman
    •  & Michael Bustin

  • Article |

    While the cytosolic translation machinery is well characterized, the mitochondrial translation system remains largely elusive. Using cryo-electron tomography, Pfeffer et al. describe the ordered organization of mitochondrial polysomes in which each ribosome is tethered to the inner membrane by two defined contacts on the large subunit in situ.

    • Stefan Pfeffer
    • , Michael W. Woellhaf
    •  & Friedrich Förster

  • Article
    | Open Access

    Mutations in GPR56, a member of the adhesion G protein-coupled receptor family, cause a specific human brain malformation and myelination defects but the cellular causes remain unclear. Here the authors show that loss of Gpr56in mice leads to decreased oligodendrocyte precursor cell proliferation and diminished levels of active RhoA.

    • Stefanie Giera
    • , Yiyu Deng
    •  & Xianhua Piao

  • Article |

    The adhesion class of G protein-coupled receptors (aGPCRs) is essential for peripheral nervous system myelination, but functions in central nervous system myelination are less understood. Here the authors show that the aGPCR Gpr56 plays a role in the development of myelinating oligodendrocytes and that this function is mediated by Gα12/13 proteins and Rho activation.

    • Sarah D. Ackerman
    • , Cynthia Garcia
    •  & Kelly R. Monk

  • Article
    | Open Access

    Ubiquitin is a stable and soluble protein, but it is commonly found in inclusion bodies in neurodegenerative disorders and cancer. Here, Morimoto et al. report that increasing ubiquitin chain length leads to the formation of amyloid-like fibrils, which are degraded by an autophagy mechanism.

    • Daichi Morimoto
    • , Erik Walinda
    •  & Masahiro Shirakawa

  • Article
    | Open Access

    TFIID is an essential transcription factor complex that controls the expression of most protein-coding genes in eukaryotes. Here the authors identify and characterize a complex containing TAF2, TAF8 and TAF10, which assembles in the cytoplasm before integration into the nuclear holo–TFIID complex.

    • Simon Trowitzsch
    • , Cristina Viola
    •  & Imre Berger

  • Article |

    NK-cell and γδ-T cell lymphoma share clinic-pathological features; however the driving mutations are largely unknown. Here the authors, using a combination of RNA-Seq analysis, targeted re-sequencing and functional analysis, identify frequent activating mutations in STAT3 and STAT5Bthat may be driver mutations in these diseases.

    • Can Küçük
    • , Bei Jiang
    •  & Wing C. Chan

  • Article |

    The little elongation complex (LEC) has been implicated in the regulation of Pol II-transcribed snRNA genes. Here, the authors show that MED26 recruits the LEC to a subset of Pol II-transcribed snRNAgenes through its N terminus, entailing a TAF7 to LEC switch that facilitates the transition from initiation to elongation.

    • Hidehisa Takahashi
    • , Ichigaku Takigawa
    •  & Shigetsugu Hatakeyama

  • Article |

    Protein fusions between the paracaspase MALT1 and API2 (inhibitor of apoptosis 2) are found in B-cell lymphoma. Here the authors identify the tumour suppressor LIMA1 as a new target of API2–MALT1 chimeric protein and show that API2–MALT1-mediated proteolysis generates a LIM domain-only (LMO)-containing fragment with oncogenic properties in vitro and in vivo.

    • Zilin Nie
    • , Ming-Qing Du
    •  & Kojo S. J. Elenitoba-Johnson

  • Article |

    Integrins are activated by binding to the cytoskeletal adaptor talin, but the mechanisms guiding activation are unclear. Here Yang et al.show that the Rap1 effector RIAM binds to the integrin-binding head of talin to promote integrin activation, perhaps by sterically interfering with talin autoinhibition.

    • Jun Yang
    • , Liang Zhu
    •  & Jun Qin

  • Article
    | Open Access

    Hypochlorous acid generated by neutrophils acts as a potent antibacterial agent. Müller et al. now show that this oxidant directly activates a protective counter-response in E. coli by N-chlorinating the protein RidA and converting it into an effective protein chaperone.

    • Alexandra Müller
    • , Sina Langklotz
    •  & Lars Ingo Ole Leichert

  • Article |

    FAN1 is a structure-specific nuclease that plays a major role in eliminating highly cytotoxic interstrand DNA crosslinks. Here, Zhao et al. present several crystal structures of FAN1 in complex with DNA substrates and biochemical analyses that establish how FAN1 functions to resolve interstrand DNA crosslinks.

    • Qi Zhao
    • , Xiaoyu Xue
    •  & Yong Xiong

  • Article
    | Open Access

    Human mitochondrial aspartate/glutamate carriers, citrin and aralar, are regulated by calcium. Here, the authors report the dimeric structure of calcium-free and -bound versions of the regulatory domains to elucidate calcium-dependent conformational changes that could regulate access of substrate to the carrier domain.

    • Chancievan Thangaratnarajah
    • , Jonathan J. Ruprecht
    •  & Edmund R. S. Kunji

  • Article
    | Open Access

    Polycystins (PC) 1 and 2 are large transmembrane proteins that play a vital role in the function of primary cilia. Here, Kim et al. identify the requirements for polycystin trafficking to the cilium, involving a PC1–PC2 interaction, PC1 proteolytic cleavage and a specific trafficking module at the trans-Golgi network.

    • Hyunho Kim
    • , Hangxue Xu
    •  & Feng Qian

  • Article
    | Open Access

    CpG islands are high GC content DNA elements that surround the majority of transcriptional start sites in eukaryotes. Here, the authors analyse over 200 genomic data sets to provide new insight into global CpG islands-dependent regulatory mechanisms in differentiated and pluripotent stem cells.

    • Samuel Beck
    • , Bum-Kyu Lee
    •  & Jonghwan Kim

  • Article |

    Cellular senescence involves extensive structural changes to chromatin, but the role of histone variants and histone cleavage is unknown. Here, Duarte et al.identify histone variant H3.3 and its proteolytically processed form lacking a portion of the N-terminal tail as key regulators of senescence.

    • Luis F. Duarte
    • , Andrew R. J. Young
    •  & Emily Bernstein

  • Article |

    The translocation and assembly module (TAM) is a nanomachine responsible for assembly of proteins into the outer membrane of pathogenic bacteria. Here, Shen et al.use magnetic contrast neutron reflectrometry to visualize movements within the TAM and insertion of a substrate protein into the lipid bilayer.

    • Hsin-Hui Shen
    • , Denisse L. Leyton
    •  & Trevor Lithgow

  • Article |

    Understanding the molecular basis of receptor activation requires characterizing the dynamic equilibrium of conformational states. Here the authors show that the metabotropic glutamate receptor oscillates between conformations on a sub-millisecond timescale, and agonists quantitatively shift the equilibrium towards the activated state based on their potency.

    • Linnea Olofsson
    • , Suren Felekyan
    •  & Emmanuel Margeat

  • Article
    | Open Access

    Integral membrane proteins laterally partition from the SecYEG translocon into the phospholipid bilayer. Here, the authors use photo-induced electron transfer to show that ribosome binding induces the opening of the lateral gate, and demonstrate that lateral opening does not happen at low temperature.

    • Yan Ge
    • , Albena Draycheva
    •  & Wolfgang Wintermeyer

  • Article |

    Opsin has recently been shown to equilibrate phospholipids across the photoreceptor disc membranes. Goren et al.demonstrate that the large conformational changes driven by exposure to light are not required for this activity, and provide insight into the potential mechanisms of lipid translocation.

    • Michael A. Goren
    • , Takefumi Morizumi
    •  & Anant K. Menon

  • Article
    | Open Access

    chTOG, a microtubule polymerase, interacts with TACC3 during mitosis to regulate spindle formation. By studying their Xenopus homologues, Mortuza et al. discover that one TACC3 recruits two chTOG molecules to the spindle, increasing its local concentration and promoting microtubule elongation.

    • Gulnahar B. Mortuza
    • , Tommaso Cavazza
    •  & Guillermo Montoya

  • Article |

    Myelination of peripheral axons by Schwann cells is essential for proper transmission of nerve signals but the underlying mechanisms are not completely understood. Here the authors show that metabolic changes are required to ensure Schwann cell differentiation and proper myelination, and involve the tumour suppressor Lkb1 in regulating this process.

    • Shabnam Pooya
    • , Xiaona Liu
    •  & Biplab Dasgupta

  • Article |

    Complexin binds to synaptic vesicles and inhibits spontaneous exocytosis. Here Snead et al. show that the high curvature of the vesicle membrane is important for membrane binding, and induces a conformational change that is important for complexin’s inhibitory function.

    • David Snead
    • , Rachel T. Wragg
    •  & David Eliezer

  • Article |

    Alpha-2-macroglobulins are protease inhibitors that function as part of eukaryotic innate immunity. Here, Wong and Dessen solve structures of Salmonella alpha-2-macroglobulin and show that it probably serves as part of a rudimentary bacterial immune system in a similar way to the eukaryotic counterpart.

    • Steve G. Wong
    •  & Andréa Dessen

  • Article |

    Membrane curvature and lipid composition direct the binding of many peripheral membrane proteins. Here, Vanni et al. use a combination of in vitroand molecular dynamics approaches to quantify how lipid-packing defects in membranes of various composition and curvature dictate the membrane adsorption of a model lipid-binding protein.

    • Stefano Vanni
    • , Hisaaki Hirose
    •  & Romain Gautier

  • Article |

    The crystal structure of the A2A GPCR suggested that water molecules might form a continuous pathway that becomes disrupted during receptor activation. Here Yuan et al.instead show that a conserved layer of hydrophobic residues forms a gate that opens to form a continuous water channel upon receptor activation.

    • Shuguang Yuan
    • , Slawomir Filipek
    •  & Horst Vogel

  • Article
    | Open Access

    The transcription factor E2F is critical for determining cell proliferation. By monitoring E2F activity in single cells throughout the cell cycle, Dong et al.provide evidence that Myc and G1 cyclin/CDKs regulate different aspects of E2F temporal dynamics, resulting in distinct phenotypic outputs.

    • Peng Dong
    • , Manoj V. Maddali
    •  & Lingchong You

  • Article |

    Following their internalization, G protein-coupled receptors may continue to signal from endosomes through downstream proteins such as Gαs. Rosciglione et al. reveal that Gαsalso regulates the onward trafficking of these receptors from endosomes to lysosomes by interacting with components of the ESCRT complex.

    • Stéphanie Rosciglione
    • , Caroline Thériault
    •  & Christine Lavoie

  • Article
    | Open Access

    G-protein coupled receptors can signal through G-proteins or through β-arrestin, however mechanisms determining pathway selection remain unclear. Here the authors show that the duration of cannabinoid receptor clustering in clathrin coated pits prior to endocytosis determines the strength of β-arrestin signalling.

    • Jacqueline Flores-Otero
    • , Kwang H. Ahn
    •  & Guillermo A. Yudowski

  • Article |

    Mutations resulting in cell transformation occur in single cells to begin with and these cells can be eliminated from epithelial layers. Here, the authors describe a mechanism whereby neighbouring normal cells mediate this extrusion using filamin and intermediate filament, vimentin.

    • Mihoko Kajita
    • , Kaoru Sugimura
    •  & Yasuyuki Fujita

  • Article |

    Some viruses possess ‘decoration’ proteins, such as gpD in lambda phage, that stabilize the viral particles in poorly understood ways. Here the authors show that gpD incorporation into lambda particles provides mechanical reinforcement and increased resistance to punctual deformations and collisions.

    • M. Hernando-Pérez
    • , S. Lambert
    •  & P. J. de Pablo

  • Article
    | Open Access

    Although many proteins adopt uneven distributions in the plasma membrane, it is not clear how these nanoscale heterogeneities relate to the general protein patterning of the membrane. Saka et al. use click chemistry to reveal the mesoscale organization of membrane proteins into multi-protein assemblies.

    • Sinem K. Saka
    • , Alf Honigmann
    •  & Silvio O. Rizzoli

  • Article |

    Despite numerous previous studies, the nature of the interaction of transcription factors (TF) with their endogenous response elements (REs) has remained unclear. Here the authors characterize the binding of p53 and glucocorticoid receptor to their endogenous REs and find that transcriptionally productive interactions are transient and involve only a small fraction of cellular TF molecules.

    • Tatsuya Morisaki
    • , Waltraud G. Müller
    •  & James G. McNally

  • Article |

    PTEN is a prominent tumour suppressor and monitoring its conformation and activity are key to developing targeted therapies. Here, the authors develop a bioluminescence resonance energy transfer biosensor for PTEN conformation and identify novel G protein-coupled receptor regulation and therapeutic activation.

    • Evelyne Lima-Fernandes
    • , Stanislas Misticone
    •  & Mark G.H. Scott

  • Article |

    It was suggested that despite the conservation of their components, yeast and human pol II initiation complexes diverged in architecture. Mühlbacher et al.now demonstrate that the yeast and human core complexes are structurally conserved and provide insight into the conformations adopted by TFIIF during initiation.

    • Wolfgang Mühlbacher
    • , Sarah Sainsbury
    •  & Patrick Cramer

  • Article |

    The study of cell membrane proteins can be simplified by incorporating them into lipid bilayers, but doing this for multiple proteins can be challenging. Here, the authors present a technique to achieve this, and show reconstitution of a bacterial respiratory chain from individual components.

    • Gustav Nordlund
    • , Peter Brzezinski
    •  & Christoph von Ballmoos

  • Article |

    The elongation factors DSIF and NELF have established roles in polymerase pausing, elongation and 3'-end processing of replication-dependent histone mRNAs. Here the authors demonstrate that DSIF and NELF form a complex with Integrator and allow proper 3'-processing of snRNA transcripts by preventing the recruitment of CstF.

    • Junichi Yamamoto
    • , Yuri Hagiwara
    •  & Yuki Yamaguchi

  • Article
    | Open Access

    Few tools are available to identify active membrane proteins within their native lipid environment. Here, Gold et al. report on a strategy that can be used for site-specific labelling of membrane proteins via electron cryotomography.

    • Vicki A.M. Gold
    • , Raffaele Ieva
    •  & Werner Kühlbrandt

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