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Membrane protein crystal structure

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https://www.readbyqxmd.com/read/28228524/structural-insights-into-the-activation-mechanism-of-dynamin-like-ehd-atpases
#1
Arthur Alves Melo, Balachandra G Hegde, Claudio Shah, Elin Larsson, J Mario Isas, Séverine Kunz, Richard Lundmark, Ralf Langen, Oliver Daumke
Eps15 (epidermal growth factor receptor pathway substrate 15)-homology domain containing proteins (EHDs) comprise a family of dynamin-related mechano-chemical ATPases involved in cellular membrane trafficking. Previous studies have revealed the structure of the EHD2 dimer, but the molecular mechanisms of membrane recruitment and assembly have remained obscure. Here, we determined the crystal structure of an amino-terminally truncated EHD4 dimer. Compared with the EHD2 structure, the helical domains are 50° rotated relative to the GTPase domain...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28226239/structural-basis-for-the-hijacking-of-endosomal-sorting-nexin-proteins-by-chlamydia-trachomatis
#2
Blessy Paul, Hyun Sung Kim, Markus C Kerr, Wilhelmina M Huston, Rohan D Teasdale, Brett M Collins
During infection chlamydial pathogens form an intracellular membrane-bound replicative niche termed the inclusion, which is enriched with bacterial transmembrane proteins called Incs. Incs bind and manipulate host cell proteins to promote inclusion expansion and provide camouflage against innate immune responses. Sorting nexin (SNX) proteins that normally function in endosomal membrane trafficking are a major class of inclusion-associated host proteins, and are recruited by IncE/CT116. Crystal structures of the SNX5 phox-homology (PX) domain in complex with IncE define the precise molecular basis for these interactions...
February 22, 2017: ELife
https://www.readbyqxmd.com/read/28220900/membrane-cholesterol-access-into-a-g-protein-coupled-receptor
#3
Ramon Guixà-González, José L Albasanz, Ismael Rodriguez-Espigares, Manuel Pastor, Ferran Sanz, Maria Martí-Solano, Moutusi Manna, Hector Martinez-Seara, Peter W Hildebrand, Mairena Martín, Jana Selent
Cholesterol is a key component of cell membranes with a proven modulatory role on the function and ligand-binding properties of G-protein-coupled receptors (GPCRs). Crystal structures of prototypical GPCRs such as the adenosine A2A receptor (A2AR) have confirmed that cholesterol finds stable binding sites at the receptor surface suggesting an allosteric role of this lipid. Here we combine experimental and computational approaches to show that cholesterol can spontaneously enter the A2AR-binding pocket from the membrane milieu using the same portal gate previously suggested for opsin ligands...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28216041/structure-of-a-type-1-secretion-system-abc-transporter
#4
Jacob L W Morgan, Justin F Acheson, Jochen Zimmer
Type-1 secretion systems (T1SSs) represent a widespread mode of protein secretion across the cell envelope in Gram-negative bacteria. The T1SS is composed of an inner-membrane ABC transporter, a periplasmic membrane-fusion protein, and an outer-membrane porin. These three components assemble into a complex spanning both membranes and providing a conduit for the translocation of unfolded polypeptides. We show that ATP hydrolysis and assembly of the entire T1SS complex is necessary for protein secretion. Furthermore, we present a 3...
February 15, 2017: Structure
https://www.readbyqxmd.com/read/28194112/physical-studies-of-p450-p450-interactions-predicting-quaternary-structures-of-p450-complexes-in-membranes-from-their-x-ray-crystal-structures
#5
REVIEW
James R Reed, Wayne L Backes
Cytochrome P450 enzymes, which catalyze oxygenation reactions of both exogenous and endogenous chemicals, are membrane bound proteins that require interaction with their redox partners in order to function. Those responsible for drug and foreign compound metabolism are localized primarily in the endoplasmic reticulum of liver, lung, intestine, and other tissues. More recently, the potential for P450 enzymes to exist as supramolecular complexes has been shown by the demonstration of both homomeric and heteromeric complexes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28194013/potent-single-domain-antibodies-that-arrest-respiratory-syncytial-virus-fusion-protein-in-its-prefusion-state
#6
Iebe Rossey, Morgan S A Gilman, Stephanie C Kabeche, Koen Sedeyn, Daniel Wrapp, Masaru Kanekiyo, Man Chen, Vicente Mas, Jan Spitaels, José A Melero, Barney S Graham, Bert Schepens, Jason S McLellan, Xavier Saelens
Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193899/structure-of-a-lipid-a-phosphoethanolamine-transferase-suggests-how-conformational-changes-govern-substrate-binding
#7
Anandhi Anandan, Genevieve L Evans, Karmen Condic-Jurkic, Megan L O'Mara, Constance M John, Nancy J Phillips, Gary A Jarvis, Siobhan S Wills, Keith A Stubbs, Isabel Moraes, Charlene M Kahler, Alice Vrielink
Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4' headgroup positions by phosphoethanolamine transferases...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193857/mass-spectrometry-based-cross-linking-study-shows-that-the-psb28-protein-binds-to-cytochrome-b559-in-photosystem-ii
#8
Daniel A Weisz, Haijun Liu, Hao Zhang, Sundarapandian Thangapandian, Emad Tajkhorshid, Michael L Gross, Himadri B Pakrasi
Photosystem II (PSII), a large pigment protein complex, undergoes rapid turnover under natural conditions. During assembly of PSII, oxidative damage to vulnerable assembly intermediate complexes must be prevented. Psb28, the only cytoplasmic extrinsic protein in PSII, protects the RC47 assembly intermediate of PSII and assists its efficient conversion into functional PSII. Its role is particularly important under stress conditions when PSII damage occurs frequently. Psb28 is not found, however, in any PSII crystal structure, and its structural location has remained unknown...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28188244/structural-intermediates-in-the-fusion-associated-transition-of-vesiculovirus-glycoprotein
#9
Eduard Baquero, Aurélie A Albertini, Hélène Raux, Abbas Abou-Hamdan, Elisabetta Boeri-Erba, Malika Ouldali, Linda Buonocore, John K Rose, Jean Lepault, Stéphane Bressanelli, Yves Gaudin
Vesiculoviruses enter cells by membrane fusion, driven by a large, low-pH-induced, conformational change in the fusion glycoprotein G that involves transition from a trimeric pre-fusion toward a trimeric post-fusion state via monomeric intermediates. Here, we present the structure of the G fusion protein at intermediate pH for two vesiculoviruses, vesicular stomatitis virus (VSV) and Chandipura virus (CHAV), which is responsible for deadly encephalopathies. First, a CHAV G crystal structure shows two intermediate conformations forming a flat dimer of heterodimers...
February 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28179147/structural-basis-of-pdz-mediated-chemokine-receptor-cxcr2-scaffolding-by-guanine-nucleotide-exchange-factor-pdz-rhogef
#10
Nicholas Spellmon, Joshua Holcomb, Andrea Niu, Vishakha Choudhary, Xiaonan Sun, Yingxue Zhang, Junmei Wan, Maysaa Doughan, Stephanie Hayden, Fatme Hachem, Joseph Brunzelle, Chunying Li, Zhe Yang
The CXC chemokine receptor 2 (CXCR2) is a G protein coupled receptor mediating interleukin-8 chemotactic signaling and plays an important role in neutrophil mobility and tumor migration. However, efficient CXCR2 signaling requires PDZ domain-mediated scaffolding of signaling complexes at the plasma membrane and functional coupling of the signaling to specific downstream signaling pathways, in which only one PDZ protein has been characterized to interact with CXCR2. Here, we identified five novel CXCR2-binding PDZ-containing proteins, among which PDZ-RhoGEF is of particular interest because this PDZ and RGS-containing guanine nucleotide exchange factor (GEF) is also involved in cell signaling and mobility...
February 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28176812/quantification-of-detergents-complexed-with-membrane-proteins
#11
Vincent Chaptal, Frédéric Delolme, Arnaud Kilburg, Sandrine Magnard, Cédric Montigny, Martin Picard, Charlène Prier, Luca Monticelli, Olivier Bornert, Morgane Agez, Stéphanie Ravaud, Cédric Orelle, Renaud Wagner, Anass Jawhari, Isabelle Broutin, Eva Pebay-Peyroula, Jean-Michel Jault, H Ronald Kaback, Marc le Maire, Pierre Falson
Most membrane proteins studies require the use of detergents, but because of the lack of a general, accurate and rapid method to quantify them, many uncertainties remain that hamper proper functional and structural data analyses. To solve this problem, we propose a method based on matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) that allows quantification of pure or mixed detergents in complex with membrane proteins. We validated the method with a wide variety of detergents and membrane proteins...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174304/the-pyruvate-and-%C3%AE-ketoglutarate-dehydrogenase-complexes-of-pseudomonas-aeruginosa-catalyze-pyocyanin-and-phenazine-1-carboxylic-acid-reduction-via-the-subunit-dihydrolipoamide-dehydrogenase
#12
Nathaniel R Glasser, Benjamin X Wang, Julie A Hoy, Dianne K Newman
Phenazines are a class of redox-active molecules produced by diverse bacteria and archaea. Many of the biological functions of phenazines, such as mediating signaling, iron acquisition, and redox homeostasis, derive from their redox activity. While prior studies have focused on extracellular phenazine oxidation by oxygen and iron, here we report a search for reductants and catalysts of intracellular phenazine reduction in Pseudomonas aeruginosa Enzymatic assays in cell-free lysate, together with crude fractionation and chemical inhibition, indicate that P...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28168783/a-novel-signal-transduction-protein-combination-of-solute-binding-and-tandem-pas-like-sensor-domains-in-one-polypeptide-chain
#13
R Wu, R Wilton, M Cuff, M Endres, G Babnigg, J N Edirisinghe, C S Henry, A Joachimiak, M Schiffer, And P R Pokkuluri
We report the structural and biochemical characterization of a novel periplasmic ligand-binding protein, Dret_0059, from Desulfohalobium retbaense DSM 5692, an organism isolated from the Salt Lake Retba in Senegal. The structure of the protein consists of a unique combination of a periplasmic solute binding protein (SBP) domain at the N-terminal and a tandem PAS-like sensor domain at the C-terminal region. SBP domains are found ubiquitously and their best known function is in solute transport across membranes...
February 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28168761/functional-clues-from-the-crystal-structure-of-an-orphan-periplasmic-ligand-binding-protein-from-treponema-pallidum
#14
Chad A Brautigam, Ranjit K Deka, Wei Z Liu, Diana R Tomchick, Michael V Norgard
The spirochete Treponema pallidum is the causative agent of syphilis, a sexually transmitted infection of major global importance. Other closely related subspecies of Treponema also are the etiological agents of the endemic treponematoses, such as yaws, pinta, and bejel. The inability of T. pallidum and its close relatives to be cultured in vitro has prompted efforts to characterize T. pallidum's proteins structurally and biophysically, particularly those potentially relevant to treponemal membrane biology, with the goal of possibly revealing the functions of those proteins...
February 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28167788/crystal-structure-of-the-adenosine-a2a-receptor-bound-to-an-antagonist-reveals-a-potential-allosteric-pocket
#15
Bingfa Sun, Priti Bachhawat, Matthew Ling-Hon Chu, Martyn Wood, Tom Ceska, Zara A Sands, Joel Mercier, Florence Lebon, Tong Sun Kobilka, Brian K Kobilka
The adenosine A2A receptor (A2AR) has long been implicated in cardiovascular disorders. As more selective A2AR ligands are being identified, its roles in other disorders, such as Parkinson's disease, are starting to emerge, and A2AR antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure of A2A receptor bound to compound 1 (Cmpd-1), a novel A2AR/N-methyl d-aspartate receptor subtype 2B (NR2B) dual antagonist and potential anti-Parkinson candidate compound, at 3...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28165484/new-insights-on-signal-propagation-by-sensory-rhodopsin-ii-transducer-complex
#16
A Ishchenko, E Round, V Borshchevskiy, S Grudinin, I Gushchin, J P Klare, A Remeeva, V Polovinkin, P Utrobin, T Balandin, M Engelhard, G Büldt, V Gordeliy
The complex of two membrane proteins, sensory rhodopsin II (NpSRII) with its cognate transducer (NpHtrII), mediates negative phototaxis in halobacteria N. pharaonis. Upon light activation NpSRII triggers a signal transduction chain homologous to the two-component system in eubacterial chemotaxis. Here we report on crystal structures of the ground and active M-state of the complex in the space group I212121. We demonstrate that the relative orientation of symmetrical parts of the dimer is parallel ("U"-shaped) contrary to the gusset-like ("V"-shaped) form of the previously reported structures of the NpSRII/NpHtrII complex in the space group P21212, although the structures of the monomers taken individually are nearly the same...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154144/gene-polymorphism-linked-to-increased-asthma-and-ibd-risk-alters-gasdermin-b-structure-a-sulfatide-and-phosphoinositide-binding-protein
#17
Kinlin L Chao, Liudmila Kulakova, Osnat Herzberg
The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively...
February 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28153808/bestrophin-1-and-retinal-disease
#18
REVIEW
Adiv A Johnson, Karina E Guziewicz, C Justin Lee, Ravi C Kalathur, Jose S Pulido, Lihua Y Marmorstein, Alan D Marmorstein
Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the "bestrophinopathies". These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago...
January 30, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28145713/electrostatic-control-of-polymorphism-in-charged-amphiphile-assemblies
#19
Changrui Gao, Honghao Li, Yue Li, Sumit Kewalramani, Liam C Palmer, Vinayak P Dravid, Samuel I Stupp, Monica Olvera de la Cruz, Michael J Bedzyk
Stimuli-induced structural transformations of molecular assemblies in aqueous solutions are integral to nanotechnological applications and biological processes. In particular, pH responsive amphiphiles as well as proteins with various degrees of ionization can reconfigure in response to pH variations. Here, we use in situ small and wide-angle X-ray scattering (SAXS/WAXS), transmission electron microscopy (TEM), and Monte Carlo simulations to show how charge regulation via pH induces morphological changes in the assembly of a positively charged peptide amphiphile (PA)...
February 10, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28143984/in-situ-tagged-nsp15-reveals-interactions-with-coronavirus-replication-transcription-complex-associated-proteins
#20
Jeremiah Athmer, Anthony R Fehr, Matthew Grunewald, Everett Clinton Smith, Mark R Denison, Stanley Perlman
: Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive...
January 31, 2017: MBio
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