Article
Biochemistry & Molecular Biology
Artem Stetsenko, Pavlo Stehantsev, Natalia O. Dranenko, Mikhail S. Gelfand, Albert Guskov
Summary: The study reports the functional and structural analysis of a membrane protein CmaX from a pathogenic Pseudomonas aeruginosa bacterium, which has a signature motif deviating from the canonical one. Despite the difference in composition, CmaX shows no changes in substrate selectivity or transport, suggesting that deviations from the canonical motif can easily alter during evolution.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biology
Swapneeta S. Date, Peng Xu, Nathaniel L. Hepowit, Nicholas S. Diab, Jordan Best, Boyang Xie, Jiale Du, Eric R. Strieter, Lauren P. Jackson, Jason A. MacGurn, Todd R. Graham
Summary: This study reveals the role of COPI in SNARE trafficking and Golgi SNARE localization through ubiquitin recognition, and demonstrates how ubiquitination enhances the binding between Arf and COPI with Gos1.
Review
Cell Biology
Hongyuan Jin, Yuanxin Tang, Liang Yang, Xueqiang Peng, Bowen Li, Qin Fan, Shibo Wei, Shuo Yang, Xinyu Li, Bo Wu, Mingyao Huang, Shilei Tang, Jingang Liu, Hangyu Li
Summary: Rab GTPases play essential roles in cancer progression by regulating membrane trafficking, and targeting Rab GTPases has the potential to become a novel approach for cancer treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
May Bakr, Damien Jullie, Julia Krapivkina, Vincent Paget-Blanc, Lou Bouit, Jennifer D. Petersen, Natacha Retailleau, Christelle Breillat, Etienne Herzog, Daniel Choquet, David Perrais
Summary: The study identifies VAMP4 as the vesicular SNARE that mediates most dendritic recycling endosome exocytosis, while VAMP2 plays a minor role in this process. Knock down of VAMP4 reduces TfR recycling but increases AMPAR recycling, leading to increased AMPAR-mediated synaptic transmission and occlusion of LTP expression. The opposing changes in AMPAR and TfR recycling upon VAMP4 knock down reveal their sorting into separate endosomal populations.
Article
Biochemistry & Molecular Biology
Anne-Florence Blandin, Elisabete Cruz Da Silva, Marie-Cecile Mercier, Oleksandr Glushonkov, Pascal Didier, Stephane Dedieu, Cristophe Schneider, Jessica Devy, Nelly Etienne-Selloum, Monique Dontenwill, Laurence Choulier, Maxime Lehmann
Summary: The study showed that EGFR TKIs induce increased EGFR accumulation in early endosomes in GBM cells, potentially altering the response of glioma cells to therapeutic treatment. Depletion of integrins can also affect the sensitivity of glioma cells to tyrosine kinase inhibitors.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Aaron M. N. Joiner, Ben P. Phillips, Kumar Yugandhar, Ethan J. Sanford, Marcus B. Smolka, Haiyuan Yu, Elizabeth A. Miller, J. Christopher Fromme
Summary: The study revealed the regulation of Rab1 activation by the TRAPPIII complex, with the Trs85 subunit serving as a membrane anchor for the entire complex via its amphipathic helix. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.
Article
Biochemical Research Methods
Laszlo Dobson, Andras Zeke, Gabor E. Tusnady
Summary: This study utilized neural networks to classify transmembrane proteins on apical and basolateral membranes, aiding in understanding drug transport and its effects. The method provided may assist researchers in identifying or characterizing molecular networks regulating the distribution of transporters or receptors.
Article
Multidisciplinary Sciences
Chiara Scaramuzzino, Emeline C. Cuoc, Patrick Pla, Sandrine Humbert, Frederic Saudou
Summary: In this study, researchers discovered that when a neurotrophin binds to its receptor in neurons, the released calcium ion is sensed by calcineurin, which triggers the retrograde movement of signaling endosomes. This finding suggests that signaling endosomes carry not only their own fuel, but also their own navigational system.
Article
Physics, Fluids & Plasmas
Ryan D. Schumm, P. C. Bressloff
Summary: The lateral diffusion and trapping of neurotransmitter receptors within the postsynaptic membrane of a neuron are crucial for synaptic strength and plasticity. This paper introduces a method to analyze the dynamics of synapses in a diffusion-trapping model of receptor trafficking, revealing the independence of steady-state synaptic weights and the influence of local accumulation times on synaptic plasticity.
Review
Plant Sciences
Guanghai Zhang, Guanghui Kong, Yongping Li
Summary: Land plants possess a unique vascular bundle system that plays a crucial role in integrating plant organs, material exchange, and signal transmission. In recent years, with the advancement of genomics and sequencing technology, there has been extensive research on the transport pathways and regulatory mechanisms of macromolecules in plants.
PHYSIOLOGIA PLANTARUM
(2021)
Article
Biochemistry & Molecular Biology
Dieter Waschbusch, Kerryn Berndsen, Pawel Lis, Axel Knebel, Yuko P. Y. Lam, Dario R. Alessi, Amir R. Khan
Summary: PPM1H acts against LRRK2 by dephosphorylating Rabs, with its flap domain identified as the specific interaction domain for Rabs. The crystal structure of PPM1H reveals a conserved phosphatase fold with a unique 110-residue flap domain, indicating an evolved mechanism for specific interaction with phosphorylated Rabs.
Review
Plant Sciences
Wen Song, Alexander Forderer, Dongli Yu, Jijie Chai
Summary: Plants use both membrane-bound and intracellular immune receptors to distinguish self from invaders, initiating pattern-triggered immunity and effector-triggered immunity respectively. Pathogens can overcome pattern-triggered immunity by secreting effectors, which are specifically recognized by intracellular NLRs receptors.
Review
Medicine, Research & Experimental
Jiayi Liu, Xuanjun Zheng, Xiaoqian Wu
Summary: This review summarizes the importance of Rab GTPase in cardiovascular diseases and suggests its potential as a therapeutic target.
Review
Immunology
Jorge Santos-Lopez, Karla de la Paz, Francisco J. Fernandez, M. Cristina Vega
Summary: The complement system plays vital roles in immune and inflammatory processes and is implicated in various human diseases. Complement receptors regulate complement-mediated immune responses and coordinate innate and adaptive immunity. Understanding the structure of complement factors and their receptor complexes is important for basic and therapeutic research.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biology
Dustin A. Ammendolia, William M. Bement, John H. Brumell
Summary: Plasma membrane integrity is crucial for cellular homeostasis, and cells have repair pathways to restore membrane integrity when damaged. Tissue-specific stressors and membrane repair pathways play important roles in health and disease. Genetic and environmental factors impact plasma membrane integrity and contribute to disease pathogenesis in various tissues.
Review
Biochemistry & Molecular Biology
Gurdeep S. Minhas, Simon Newstead
BIOCHEMICAL SOCIETY TRANSACTIONS
(2020)
Article
Cell Biology
Michela Serena, Ricardo Nunes Bastos, Paul R. Elliott, Francis A. Barr
JOURNAL OF CELL BIOLOGY
(2020)
Article
Biochemical Research Methods
Iwan Zimmermann, Pascal Egloff, Cedric A. J. Hutter, Benedikt T. Kuhn, Philipp Brauer, Simon Newstead, Roger J. P. Dawson, Eric R. Geertsma, Markus A. Seeger
Article
Multidisciplinary Sciences
Zhiyi Wu, Simon Newstead, Philip C. Biggin
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Gabriel Kuteyi, Zhiyi Wu, Jiandong Huo, I. David Goldman, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: Folates, also known as vitamin B9, play a critical role in cellular metabolism and their deficiency is linked to various disorders. Mammals cannot synthesize folates and rely on uptake from the diet. The proton-coupled folate transporter is important for folate uptake and drug delivery.
Article
Biochemistry & Molecular Biology
Oliver Adams, Justin C. Deme, Joanne L. Parker, Philip W. Fowler, Susan M. Lea, Simon Newstead
Summary: The structure analysis of Mtb MmpL3 can help us understand the mechanism of drug resistance mutations, revealing the positioning of resistance variants at the drug binding site, and also highlighting a potential alternative route to resistance within the periplasmic domain.
Article
Biology
Andreas Gerondopoulos, Philipp Brauer, Tomoaki Sobajima, Zhiyi Wu, Joanne L. Parker, Philip Biggin, Francis A. Barr, Simon Newstead
Summary: The study investigates the selective retrieval of ER proteins by the KDEL receptor, revealing a dynamic process of signal capture as it enters the binding pocket. Additionally, it uncovers the affinity differences between HDEL and KDEL, attributing the discrepancy to interactions between specific residues at the -4 position of the signal and residues in the receptor binding pocket.
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Zhiyi Wu, Gabriel Kuteyi, Jiandong Huo, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: The proton-coupled solute carriers PepT1 and PepT2 in the SLC15 family are crucial for acquiring dietary nitrogen and have extreme substrate promiscuity. Recent studies on their structure and function provide insights into their potential applications in drug development.
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Dimitrios Kolokouris, Gabriel Kuteyi, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: The study presents the cryo-EM structure of human system xc- in both apo and glutamate bound states, discussing its cystine transport mechanism and highlighting its potential as a target for anticancer therapies due to its role in cellular redox homeostasis. The research shows an allosteric mechanism for ligand discrimination in system xc(-) supported by molecular dynamics and cell-based assays, establishing a mechanism for cystine transport in human cells.
NATURE COMMUNICATIONS
(2021)
Article
Biophysics
Chenghan Li, Zhi Yue, Simon Newstead, Gregory A. Voth
Summary: This study uses multiscale modeling to investigate the functional cycle of proton-coupled peptide transporters (POTs), providing computational confirmation for the alternating access model and a quantitative multiscale kinetic picture of the functioning protein mechanism.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Simon Newstead
Summary: Structural studies on mammalian vitamin transport, especially folates, are lagging behind other metabolites. This study focuses on the three different systems responsible for folate uptake in the human body and the potential of targeting specific folate transporters for developing new antifolates with improved pharmacology. Recent findings on the proton-coupled folate transporter provide insights into antifolate recognition and the mechanism of transport, which, combined with previous knowledge on folate receptors and predictions for the structure of the reduced folate carrier, contribute to the acceleration of antifolate drug development.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joanne L. Parker, Takafumi Kato, Gabriel Kuteyi, Oleg Sitsel, Simon Newstead
Summary: The kidney in mammals maintains blood homeostasis by selectively taking up, retaining or eliminating toxins, drugs and metabolites. Organic anion transporters (OATs) are responsible for recognizing and excreting metabolites and toxins in the nephron. Inhibition of OATs is therapeutically used to enhance drug efficacy and reduce nephrotoxicity. This study presents cryogenic-electron microscopy structures of OAT1 bound to alpha-ketoglutarate, tenofovir, and probenecid, providing molecular insights into alpha-ketoglutarate driven drug elimination and the allosteric regulation of organic anion transport by chloride in the kidney.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Elena Poser, Renaud Caous, Ulrike Gruneberg, Francis A. Barr
JOURNAL OF CELL BIOLOGY
(2020)