Article
|
Open Access
Featured
-
-
Article
| Open AccessLigand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors
The serotonin transporter, targeted by several medications, terminates neurotransmission by clearing serotonin from the synaptic cleft. Combining biochemical results with in silico data, the authors show the key interactions that initiate substrate transport.
- Ralph Gradisch
- , Katharina Schlögl
- & Thomas Stockner
-
Article
| Open AccessStructural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP2
BTR1 is an electrogenic H+ transporter belonging to the bicarbonate transporter family. Here, the authors present structures of BTR1 in different conformations and uncover PIP2 as the activator of BTR1.
- Yishuo Lu
- , Peng Zuo
- & Yuxin Yin
-
Article
| Open AccessIncreased renal elimination of endogenous and synthetic pyrimidine nucleosides in concentrative nucleoside transporter 1 deficient mice
Concentrative nucleoside transporters (CNTs) are cellular nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here the authors show a role of CNT1 in the renal reabsorption of endogenous and synthetic nucleosides.
- Avinash K. Persaud
- , Matthew C. Bernier
- & Rajgopal Govindarajan
-
Article
| Open AccessStructural basis for functional interactions in dimers of SLC26 transporters
The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. Here, the authors resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize it by PELDOR/DEER distance measurements, biochemical studies with MD simulations and spin-label ensemble refinement.
- Yung-Ning Chang
- , Eva A. Jaumann
- & Eric R. Geertsma
-
Article
| Open AccessBroad phylogenetic analysis of cation/proton antiporters reveals transport determinants
Cation/proton antiporters (CPAs) play a major role in maintaining living cells’ homeostasis and are divided in two main groups: CPA1 and CPA2. Here authors use a comprehensive evolutionary analysis of 6537 representative CPAs and reveal a sequence motif that determines central phenotypic characteristics.
- Gal Masrati
- , Manish Dwivedi
- & Nir Ben-Tal
-
Article
| Open AccessAXER is an ATP/ADP exchanger in the membrane of the endoplasmic reticulum
Endoplasmic reticulum (ER) functioning requires a constant supply of ATP, but the exchanger required for ATP uptake into the ER is unknown. Here, the authors report that SLC35B1, here named AXER, or ATP/ADP exchanger into the ER, can transport ATP into the ER.
- Marie-Christine Klein
- , Katharina Zimmermann
- & Ilka Haferkamp
-
Article
| Open AccessAllosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19
PEX19 is a chaperone and import receptor for peroxisomal membrane proteins (PMPs). Here the authors present the structure of the farnesylated C-terminal domain of PEX19, and its interaction with PMPs reveals how the farnesyl moiety allosterically reshapes the PMP binding surface and modulates PEX19 function.
- Leonidas Emmanouilidis
- , Ulrike Schütz
- & Michael Sattler
-
Article
| Open AccessStructural basis of transcobalamin recognition by human CD320 receptor
Cellular uptake of vitamin B12 (cobalamin) requires the binding of holo-transcobalamin (TC) from plasma by CD320. Here, the authors report the structure of a complex between CD320 and TC loaded with cyanocobalamin, alongside additional functional analysis.
- Amer Alam
- , Jae-Sung Woo
- & Kaspar P. Locher
-
Article
| Open AccessTranslation control during prolonged mTORC1 inhibition mediated by 4E-BP3
The eIF4E-binding proteins (4E-BPs) are critical repressors of cap-dependent translation via mTOR, a pathway frequently hyperactivated in cancer. Here the authors show that 4E-BP3 specifically mediates the cap-dependent translation repression and antiproliferative effects of prolonged pharmacological mTOR inhibition.
- Yoshinori Tsukumo
- , Tommy Alain
- & Nahum Sonenberg
-
Article
| Open AccessStructure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A
Xpo4 imports Sox2 and other proteins into the cell nucleus, while exporting eIF5A or Smad3; how it recognizes these proteins has been unclear. Here, the authors solved the crystal structure of the RanGTP, Xpo4 and eIF5A complex and investigate how Xpo4 identifies its major export cargo.
- Metin Aksu
- , Sergei Trakhanov
- & Dirk Görlich
-
Article
| Open AccessNdfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells
Ndfip1 is an activator of Itch E3 ubiquitin ligase that limits T cell activation. Here the authors identify Jak1 in a proteomic screen for Ndfip dependent substrates, and show that Ndfip1/2 double-deficient T cells have reduced degradation of Jak1 and as a result are hyper-responsive to cytokine stimulation.
- Claire E. O’Leary
- , Christopher R. Riling
- & Paula M. Oliver
-
Article
| Open AccessStructure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity
UapA is a uric acid/xanthine H+symporter from a filamentous fungus. Here, the authors solve the crystal structure of the transporter in complex with xanthine revealing it to be a dimer, and this homodimerisation is proposed to be important for function.
- Yilmaz Alguel
- , Sotiris Amillis
- & Bernadette Byrne
-
Article
| Open AccessDifferent states of synaptotagmin regulate evoked versus spontaneous release
Synaptotagmin contains tandem Ca2+-binding C2-domains that interact with target membranes to trigger exocytosis. Here, Bai et al. manipulate the relative orientation of these two domains using a synthetic polyproline linker and show that a parallel orientation is most effective for membrane interaction and exocytosis.
- Hua Bai
- , Renhao Xue
- & Edwin R. Chapman
-
Article
| Open AccessCiliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation
Primary cilia are highly conserved microtubule-based organelles that play essential roles in several cellular processes including osteogenesis. Here the authors show that intraflagellar protein IFT80 regulates osteoblast differentiation by balancing signalling though the canonical and non-canonical Hedgehog pathways.
- Xue Yuan
- , Jay Cao
- & Shuying Yang
-
Article
| Open AccessA resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement
Amoeboid motility is driven by actomyosin-based contraction and exploits differences in the mechanical properties of the cortical cytoskeleton. Here the authors discover that mDia1-like formin A is responsible for generating a subset of actin filaments at the rear of Dictyosteliumthat suppresses lateral protrusions and blebbing during 2D-confined migration.
- Nagendran Ramalingam
- , Christof Franke
- & Jan Faix
-
Article
| Open AccessCalcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers
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 AccessAnnexin-A5 assembled into two-dimensional arrays promotes cell membrane repair
Eukaryotic cell plasma membranes possess a mechanism to repair tears caused by stimuli such as mechanical stress. The authors demonstrate that annexin-A5, when assembled into two-dimensional arrays in the presence of calcium, is required for membrane repair.
- Anthony Bouter
- , Céline Gounou
- & Alain R. Brisson
-
Article
| Open AccessDisruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity
Thioredoxin binding protein-2 (TBP-2) mutant mice have abnormal insulin sensitivity and secretion. In this study, TBP-2-null obese mice are shown to have improved insulin sensitivity and glucose intolerance, suggesting a potential role for TBP-2 inhibition in diabetes treatment.
- Eiji Yoshihara
- , Shimpei Fujimoto
- & Hiroshi Masutani