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Membrane protein crystal structure

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https://www.readbyqxmd.com/read/28716648/applications-of-high-speed-atomic-force-microscopy-to-real-time-visualization-of-dynamic-biomolecular-processes
#1
REVIEW
Takayuki Uchihashi, Simon Scheuring
BACKGROUND: Many biological processes in a living cell are consequences of sequential and hierarchical dynamic events of biological macromolecules such as molecular interactions and conformational changes. Hence, knowledge of structures, assembly and dynamics of proteins is the foundation for understanding how biological molecules work. Among several techniques to analyze dynamics of proteins, high-speed atomic force microscopy (HS-AFM) is unique to provide direct information about both structure and dynamics of single proteins at work...
July 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28714993/a-two-helix-motif-positions-the-lysophosphatidic-acid-acyltransferase-active-site-for-catalysis-within-the-membrane-bilayer
#2
Rosanna M Robertson, Jiangwei Yao, Stefan Gajewski, Gyanendra Kumar, Erik W Martin, Charles O Rock, Stephen W White
Phosphatidic acid (PA), the central intermediate in membrane phospholipid synthesis, is generated by two acyltransferases in a pathway conserved in all life forms. The second step in this pathway is catalyzed by 1-acyl-sn-glycerol-3-phosphate acyltransferase, called PlsC in bacteria. Here we present the crystal structure of PlsC from Thermotoga maritima, revealing an unusual hydrophobic/aromatic N-terminal two-helix motif linked to an acyltransferase αβ-domain that contains the catalytic HX4D motif. PlsC dictates the acyl chain composition of the 2-position of phospholipids, and the acyl chain selectivity 'ruler' is an appropriately placed and closed hydrophobic tunnel...
July 17, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28714967/architecture-of-the-type-iv-coupling-protein-complex-of-legionella-pneumophila
#3
Mi-Jeong Kwak, J Dongun Kim, Hyunmin Kim, Cheolhee Kim, James W Bowman, Seonghoon Kim, Keehyoung Joo, Jooyoung Lee, Kyeong Sik Jin, Yeon-Gil Kim, Nam Ki Lee, Jae U Jung, Byung-Ha Oh
Many bacteria, including Legionella pneumophila, rely on the type IV secretion system to translocate a repertoire of effector proteins into the hosts for their survival and growth. Type IV coupling protein (T4CP) is a hexameric ATPase that links translocating substrates to the transenvelope secretion conduit. Yet, how a large number of effector proteins are selectively recruited and processed by T4CPs remains enigmatic. DotL, the T4CP of L. pneumophila, contains an ATPase domain and a C-terminal extension whose function is unknown...
July 17, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28712807/snx16-regulates-the-recycling-of-e-cadherin-through-a-unique-mechanism-of-coordinated-membrane-and-cargo-binding
#4
Jinxin Xu, Leilei Zhang, Yinghua Ye, Yongli Shan, Chanjuan Wan, Junfeng Wang, Duanqing Pei, Xiaodong Shu, Jinsong Liu
E-Cadherin is a major component of adherens junctions on cell surfaces. SNX16 is a unique member of sorting nexins that contains a coiled-coil (CC) domain downstream of the PX domain. We report here that SNX16 regulates the recycling trafficking of E-cadherin. We solved the crystal structure of PX-CC unit of SNX16 and revealed a unique shear shaped homodimer. We identified a novel PI3P binding pocket in SNX16 that consists of both the PX and the CC domains. Surprisingly, we showed that the PPII/α2 loop, which is generally regarded as a membrane insertion loop in PX family proteins, is involved in the E-cadherin binding with SNX16...
July 11, 2017: Structure
https://www.readbyqxmd.com/read/28712723/msp1-is-a-membrane-protein-dislocase-for-tail-anchored-proteins
#5
Matthew L Wohlever, Agnieszka Mateja, Philip T McGilvray, Kasey J Day, Robert J Keenan
Mislocalized tail-anchored (TA) proteins of the outer mitochondrial membrane are cleared by a newly identified quality control pathway involving the conserved eukaryotic protein Msp1 (ATAD1 in humans). Msp1 is a transmembrane AAA-ATPase, but its role in TA protein clearance is not known. Here, using purified components reconstituted into proteoliposomes, we show that Msp1 is both necessary and sufficient to drive the ATP-dependent extraction of TA proteins from the membrane. A crystal structure of the Msp1 cytosolic region modeled into a ring hexamer suggests that active Msp1 contains a conserved membrane-facing surface adjacent to a central pore...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28710286/how-tetraspanins-shape-endothelial-and-leukocyte-nano-architecture-during-inflammation
#6
REVIEW
Jonas Franz, Marco Tarantola, Christoph Riethmüller
Tetraspanins are ubiquitous membrane proteins that induce local membrane curvature and hence co-ordinate cell-to-cell contacts. This review highlights their role in inflammation, which requires control of the nano-architecture of attachment sites between endothelial cells and leukocytes. The active role of endothelial cells in preparing for transmigration of leukocytes and determining the severity of an inflammation is often underscored. A clear hint to endothelial pre-activation is their ability to protrude clustered adhesion proteins upward prior to leukocyte contact...
July 14, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28704713/cation-chelation-and-ph-induced-controlled-switching-of-the-non-fouling-properties-of-bacterial-crystalline-films
#7
Jagoba Iturri, Alberto Moreno-Cencerrado, José L Toca-Herrera
We report the controlled loss of the anti-fouling activity of the S-layer protein SbpA from Lysinibacillus sphaericus (CCM2177). This protein forms crystal-like films with square lattice (p4) via self-assembly on almost any type of surfaces. Such engineered bioinspired nanometric membranes are known by their excellent preventive performance under biological conditions. However, their exposure to certain treatments can lead to gradual degradation of the S-protein layer. In this work, two distinctive approaches are studied for understanding either specific or non-specific degradation of the film, by treatment with a chelating agent (EDTA), which interacts with inner Ca(2+) ions, or Citrate buffer (with pH<pI), respectively...
July 3, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28701415/structure-of-psd-95-map1a-complex-reveals-unique-target-recognition-mode-of-maguk-gk-domain
#8
Yitan Xia, Yuan Shang, Rongguang Zhang, Jinwei Zhu
The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodeling which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), though the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing...
July 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28698362/structural-insights-into-lipoprotein-n-acylation-by-escherichia-coli-apolipoprotein-n-acyltransferase
#9
Cameron L Noland, Michele D Kattke, Jingyu Diao, Susan L Gloor, Homer Pantua, Mike Reichelt, Anand K Katakam, Donghong Yan, Jing Kang, Inna Zilberleyb, Min Xu, Sharookh B Kapadia, Jeremy M Murray
Gram-negative bacteria express a diverse array of lipoproteins that are essential for various aspects of cell growth and virulence, including nutrient uptake, signal transduction, adhesion, conjugation, sporulation, and outer membrane protein folding. Lipoprotein maturation requires the sequential activity of three enzymes that are embedded in the cytoplasmic membrane. First, phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (Lgt) recognizes a conserved lipobox motif within the prolipoprotein signal sequence and catalyzes the addition of diacylglycerol to an invariant cysteine...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695856/crystal-structure-of-yersinia-pestis-virulence-factor-yfea-reveals-two-polyspecific-metal-binding-sites
#10
Christopher D Radka, Lawrence J DeLucas, Landon S Wilson, Matthew B Lawrenz, Robert D Perry, Stephen G Aller
Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. In Yersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels...
July 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28694191/on-the-role-of-subunit-m-in-cytochrome-cbb3-oxidase
#11
Catarina A Carvalheda, Andrei V Pisliakov
Cytochrome cbb3 (or C-type) oxidases are a highly divergent group and the least studied members of the heme-copper oxidases (HCOs) superfamily. HCOs couple the reduction of oxygen at the end of the respiratory chain to the active proton translocation across the membrane, contributing to establishment of an electrochemical gradient essential for ATP synthesis. Cbb3 oxidases exhibit unique structural and functional features and have an essential role in the metabolism of many clinically relevant human pathogens...
July 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28691777/structure-and-evolution-of-enth-and-vhs-enth-like-domains-in-tepsin
#12
Tara L Archuleta, Meredith N Frazier, Anderson E Monken, Amy K Kendall, Joel Harp, Airlie J McCoy, Nicole Creanza, Lauren P Jackson
Tepsin is currently the only accessory trafficking protein identified in adaptor-related protein 4 (AP4) coated vesicles originating at the trans-Golgi network (TGN). The molecular basis for interactions between AP4 subunits and motifs in the tepsin C-terminus have been characterized, but the biological role of tepsin remains unknown. We determined X-ray crystal structures of the tepsin ENTH and VHS/ENTH-like domains. Our data reveal unexpected structural features that suggest key functional differences between these and similar domains in other trafficking proteins...
July 10, 2017: Traffic
https://www.readbyqxmd.com/read/28684785/identification-of-histamine-h3-receptor-ligands-using-a-new-crystal-structure-fragment-based-method
#13
Ida Osborn Frandsen, Michael W Boesgaard, Kimberley Fidom, Alexander S Hauser, Vignir Isberg, Hans Bräuner-Osborne, Petrine Wellendorph, David E Gloriam
Virtual screening offers an efficient alternative to high-throughput screening in the identification of pharmacological tools and lead compounds. Virtual screening is typically based on the matching of target structures or ligand pharmacophores to commercial or in-house compound catalogues. This study provides the first proof-of-concept for our recently reported method where pharmacophores are instead constructed based on the inference of residue-ligand fragments from crystal structures. We demonstrate its unique utility for G protein-coupled receptors, which represent the largest families of human membrane proteins and drug targets...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682624/characterisation-of-the-escherichia-coli-concentrative-nucleoside-transporter-nupc-using-computational-biochemical-and-biophysical-methods
#14
Lijie Sun, Hao Xie, Jean C Ingram, Ryan J Hope, Stephen A Baldwin, Simon G Patching
The concentrative nucleoside transporter (CNT) family of proteins mediate uptake of nucleosides into cells driven by a cation gradient, which then enter salvage pathways for nucleic acid synthesis. In humans they also transport hydrophilic anti-cancer and anti-viral nucleoside analogue drugs into cells and tissues where they exert their pharmacological effects. Escherichia coli CNT NupC (400 residues) is pyrimidine-specific and driven by a proton gradient. We have used computational, biochemical and biophysical methods to characterise evolutionary relationships, conservation of residues, structural domains, transmembrane helices and residues involved in nucleoside binding and/or transport activity in NupC compared with sodium-driven Vibrio cholerae CNT (vcCNT) and human CNTs (hCNT1-3)...
July 6, 2017: Biochemistry
https://www.readbyqxmd.com/read/28669632/regulation-of-the-equilibrium-between-closed-and-open-conformations-of-annexin-a2-by-n-terminal-phosphorylation-and-s100a4-binding
#15
Péter Ecsédi, Bence Kiss, Gergő Gógl, László Radnai, László Buday, Kitti Koprivanacz, Károly Liliom, Ibolya Leveles, Beáta Vértessy, Norbert Jeszenői, Csaba Hetényi, Gitta Schlosser, Gergely Katona, László Nyitray
Annexin A2 (ANXA2) has a versatile role in membrane-associated functions including membrane aggregation, endo- and exocytosis, and it is regulated by post-translational modifications and protein-protein interactions through the unstructured N-terminal domain (NTD). Our sequence analysis revealed a short motif responsible for clamping the NTD to the C-terminal core domain (CTD). Structural studies indicated that the flexibility of the NTD and CTD are interrelated and oppositely regulated by Tyr24 phosphorylation and Ser26Glu phosphomimicking mutation...
June 21, 2017: Structure
https://www.readbyqxmd.com/read/28666141/computational-design-of-peptide-ligands-to-target-the-intermolecular-interaction-between-viral-envelope-protein-and-pediatric-receptor
#16
Darong Xu, Hongliang Bian, Jinlan Cai, Daocheng Bao, Qing Jin, Min Zhu, Cuifeng Zhang, Tingting Tao
The recognition and binding of viral envelope protein to pediatric receptor subverts the membrane-trafficking apparatus to mediate virion export in young children. Here, we described a successful computational design of peptide ligands to target the intermolecular interaction between the virus large envelope protein (LHB) and adaptin receptor (ADT). Based on the crystal structure of ADT in complex with an oligopeptide segment corresponding to the core binding site of LHB, a sequence-specific amino acid preference profile was determined systematically for the ADT-binding peptides using structural bioinformatics approach...
June 17, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28657745/recent-advances-in-structure-based-drug-design-targeting-class-a-g-protein-coupled-receptors-utilizing-crystal-structures-and-computational-simulations
#17
Yoonji Lee, Shaherin Basith, Sun Choi
G protein-coupled receptors (GPCRs) represent the largest and most physiologically important integral membrane protein family, and these receptors respond to a wide variety of physiological and environmental stimuli. GPCRs are among the most critical therapeutic targets for numerous human diseases, and approximately one-third of the currently marketed drugs target this receptor family. The recent breakthroughs in GPCR structural biology have significantly contributed to our understanding of GPCR function, ligand binding, and pharmacological action as well as to the design of new drugs...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28652409/interaction-between-the-ph-and-start-domains-of-ceramide-transfer-protein-competes-with-phosphatidylinositol-4-phosphate-binding-by-the-ph-domain
#18
Jennifer Prashek, Samuel Bouyain, Mingui Fu, Yong Li, Dusan Berkes, Xiaolan Yao
De novo synthesis of the sphingolipid sphingomyelin requires non-vesicular transport of ceramide from the endoplasmic reticulum to the Golgi by the multidomain protein ceramide transfer protein (CERT). CERT's N-terminal pleckstrin homology (PH) domain targets it to the Golgi by binding to phosphatidylinositol 4-phosphate (PtdIns(4)P) in the Golgi membrane, while its C-terminal StAR-related lipid transfer domain (START) carries out ceramide transfer. Hyper-phosphorylation of a serine rich (SR) motif immediately following the PH domain decreases both PtdIns(4)P binding and ceramide transfer by CERT...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28650463/type-vi-secretion-tssk-baseplate-protein-exhibits-structural-similarity-with-phage-receptor-binding-proteins-and-evolved-to-bind-the-membrane-complex
#19
Van Son Nguyen, Laureen Logger, Silvia Spinelli, Pierre Legrand, Thi Thanh Huyen Pham, Thi Trang Nhung Trinh, Yassine Cherrak, Abdelrahim Zoued, Aline Desmyter, Eric Durand, Alain Roussel, Christine Kellenberger, Eric Cascales, Christian Cambillau
The type VI secretion system (T6SS) is a multiprotein machine widespread in Gram-negative bacteria that delivers toxins into both eukaryotic and prokaryotic cells. The mechanism of action of the T6SS is comparable to that of contractile myophages. The T6SS builds a tail-like structure made of an inner tube wrapped by a sheath, assembled under an extended conformation. Contraction of the sheath propels the inner tube towards the target cell. The T6SS tail is assembled on a platform-the baseplate-which is functionally similar to bacteriophage baseplates...
June 26, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28650154/interrogating-detergent-desolvation-of-nanopore-forming-proteins-by-fluorescence-polarization-spectroscopy
#20
Aaron J Wolfe, Yi-Ching Hsueh, Adam R Blanden, Mohammad M Mohammad, Bach Pham, Avinash K Thakur, Stewart N Loh, Min Chen, Liviu Movileanu
Understanding how membrane proteins interact with detergents is of fundamental and practical significance in structural and chemical biology as well as in nanobiotechnology. Current methods for inspecting protein-detergent complex (PDC) interfaces require high concentrations of protein and are of low throughput. Here, we describe a scalable, spectroscopic approach that uses nanomolar protein concentrations in native solutions. This approach, which is based on steady-state fluorescence polarization (FP) spectroscopy, kinetically resolves the dissociation of detergents from membrane proteins and protein unfolding...
July 10, 2017: Analytical Chemistry
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