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Biochimica Et Biophysica Acta Sep 2015Cell membranes are composed of a lipid bilayer containing proteins that cross and/or interact with lipids on either side of the two leaflets. The basic structure of cell... (Review)
Review
Cell membranes are composed of a lipid bilayer containing proteins that cross and/or interact with lipids on either side of the two leaflets. The basic structure of cell membranes is this bilayer, composed of two opposing lipid monolayers with fascinating properties designed to perform all the functions the cell requires. To coordinate these functions, lipid composition of cellular membranes is tailored to suit their specialized tasks. In this review, we describe the general mechanisms of membrane-protein interactions and relate them to some of the molecular strategies organisms use to adjust the membrane lipid composition in response to a decrease in environmental temperature. While the activities of all biomolecules are altered as a function of temperature, the thermosensors we focus on here are molecules whose temperature sensitivity appears to be linked to changes in the biophysical properties of membrane lipids. This article is part of a Special Issue entitled: Lipid-protein interactions.
Topics: Animals; Humans; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Models, Molecular; Protein Binding; Protein Structure, Tertiary; Temperature; Thermosensing
PubMed: 25906947
DOI: 10.1016/j.bbamem.2015.04.005 -
Journal of Molecular Biology Mar 2015The biogenesis, folding, and structure of α-helical membrane proteins (MPs) are important to understand because they underlie virtually all physiological processes in... (Review)
Review
The biogenesis, folding, and structure of α-helical membrane proteins (MPs) are important to understand because they underlie virtually all physiological processes in cells including key metabolic pathways, such as the respiratory chain and the photosystems, as well as the transport of solutes and signals across membranes. Nearly all MPs require translocons--often referred to as protein-conducting channels--for proper insertion into their target membrane. Remarkable progress toward understanding the structure and functioning of translocons has been made during the past decade. Here, we review and assess this progress critically. All available evidence indicates that MPs are equilibrium structures that achieve their final structural states by folding along thermodynamically controlled pathways. The main challenge for cells is the targeting and membrane insertion of highly hydrophobic amino acid sequences. Targeting and insertion are managed in cells principally by interactions between ribosomes and membrane-embedded translocons. Our review examines the biophysical and biological boundaries of MP insertion and the folding of polytopic MPs in vivo. A theme of the review is the under-appreciated role of basic thermodynamic principles in MP folding and assembly. Thermodynamics not only dictates the final folded structure but also is the driving force for the evolution of the ribosome-translocon system of assembly. We conclude the review with a perspective suggesting a new view of translocon-guided MP insertion.
Topics: Cell Membrane; Membrane Proteins; Protein Folding; Protein Structure, Tertiary; Ribosomes; Thermodynamics
PubMed: 25277655
DOI: 10.1016/j.jmb.2014.09.014 -
The Journal of Biological Chemistry 2021Biological membranes define the boundaries of cells and compartmentalize the chemical and physical processes required for life. Many biological processes are carried out... (Review)
Review
Biological membranes define the boundaries of cells and compartmentalize the chemical and physical processes required for life. Many biological processes are carried out by proteins embedded in or associated with such membranes. Determination of membrane protein (MP) structures at atomic or near-atomic resolution plays a vital role in elucidating their structural and functional impact in biology. This endeavor has determined 1198 unique MP structures as of early 2021. The value of these structures is expanded greatly by deposition of their three-dimensional (3D) coordinates into the Protein Data Bank (PDB) after the first atomic MP structure was elucidated in 1985. Since then, free access to MP structures facilitates broader and deeper understanding of MPs, which provides crucial new insights into their biological functions. Here we highlight the structural and functional biology of representative MPs and landmarks in the evolution of new technologies, with insights into key developments influenced by the PDB in magnifying their impact.
Topics: Databases, Protein; History, 20th Century; History, 21st Century; Membrane Proteins; Protein Conformation; Structure-Activity Relationship
PubMed: 33744283
DOI: 10.1016/j.jbc.2021.100557 -
Biochimica Et Biophysica Acta.... Sep 2022Non-ionic detergents are important tools for the investigation of interactions between membrane proteins and lipid membranes. Recent studies led to the question as to...
Non-ionic detergents are important tools for the investigation of interactions between membrane proteins and lipid membranes. Recent studies led to the question as to whether the ability to capture protein-lipid interactions depends on the properties of detergents or their concentration in purification buffers. To address this question, we present the synthesis of an asymmetric, hybrid detergent that combines the head groups of detergents with opposing delipidating properties. We discuss detergent properties and protein purification outcomes to reveal whether the properties of detergent micelles or the detergent concentration in purification buffers drive membrane protein delipidation. We anticipate that our findings will enable the development of rationally design detergents for future applications in membrane protein research.
Topics: Detergents; Lipids; Membrane Proteins; Micelles
PubMed: 35551920
DOI: 10.1016/j.bbamem.2022.183958 -
Current Opinion in Structural Biology Oct 2019Solving high-resolution structures of membrane proteins has been an important challenge for decades, still lagging far behind that of soluble proteins even with the... (Review)
Review
Solving high-resolution structures of membrane proteins has been an important challenge for decades, still lagging far behind that of soluble proteins even with the recent remarkable technological advances in X-ray crystallography and electron microscopy. Central to this challenge is the necessity to isolate and solubilize membrane proteins in a stable, natively folded and functional state, a process influenced by not only the proteins but also their surrounding chemical environment. This review highlights recent community efforts in the development and characterization of novel membrane agents and ligand tools to stabilize individual proteins and protein complexes, which together have accelerated progress in membrane protein structural biology.
Topics: Crystallization; Detergents; Membrane Proteins; Protein Stability; Solubility
PubMed: 31285102
DOI: 10.1016/j.sbi.2019.06.002 -
ELife Nov 2022TMEM87s are eukaryotic transmembrane proteins with two members (TMEM87A and TMEM87B) in humans. TMEM87s have proposed roles in protein transport to and from the Golgi,...
TMEM87s are eukaryotic transmembrane proteins with two members (TMEM87A and TMEM87B) in humans. TMEM87s have proposed roles in protein transport to and from the Golgi, as mechanosensitive ion channels, and in developmental signaling. TMEM87 disruption has been implicated in cancers and developmental disorders. To better understand TMEM87 structure and function, we determined a cryo-EM structure of human TMEM87A in lipid nanodiscs. TMEM87A consists of a Golgi-dynamics (GOLD) domain atop a membrane-spanning seven-transmembrane helix domain with a large cavity open to solution and the membrane outer leaflet. Structural and functional analyses suggest TMEM87A may not function as an ion channel or G-protein coupled receptor. We find TMEM87A shares its characteristic domain arrangement with seven other proteins in humans; three that had been identified as evolutionary related (TMEM87B, GPR107, and GPR108) and four previously unrecognized homologs (GPR180, TMEM145, TMEM181, and WLS). Among these structurally related LD domain even-ransmembrane helix (GOST) proteins, WLS is best characterized as a membrane trafficking and secretion chaperone for lipidated Wnt signaling proteins. We find key structural determinants for WLS function are conserved in TMEM87A. We propose TMEM87A and structurally homologous GOST proteins could serve a common role in trafficking membrane-associated cargo.
Topics: Humans; Golgi Apparatus; Protein Transport; Membrane Proteins; Receptors, G-Protein-Coupled; Family
PubMed: 36373655
DOI: 10.7554/eLife.81704 -
Autophagy Nov 2020Several studies have provided insight into the unique intracellular localization, dynamic trafficking and diverse repertoire of binding partners of Atg9/ATG9, but...
Several studies have provided insight into the unique intracellular localization, dynamic trafficking and diverse repertoire of binding partners of Atg9/ATG9, but structural details of the protein have remained elusive. Guardia and colleagues now report the structure of human ATG9A to a resolution of 2.9 Å, revealing, among other features, an elaborate system of tunnels permeating the ATG9A protein complex.
Topics: Autophagosomes; Autophagy; Autophagy-Related Proteins; Humans; Membrane Proteins; Protein Transport; Vesicular Transport Proteins
PubMed: 32840139
DOI: 10.1080/15548627.2020.1810901 -
Emerging Topics in Life Sciences Nov 2021Membrane proteins, found at the junctions between the outside world and the inner workings of the cell, play important roles in human disease and are used as biosensors....
Membrane proteins, found at the junctions between the outside world and the inner workings of the cell, play important roles in human disease and are used as biosensors. More than half of all therapeutics directly affect membrane protein function while nanopores enable DNA sequencing. The structural and functional characterisation of membrane proteins is therefore crucial. However, low levels of naturally abundant protein and the hydrophobic nature of membrane proteins makes production difficult. To maximise success, high-throughput strategies were developed that rely upon simple screens to identify successful constructs and rapidly exclude those unlikely to work. Parameters that affect production such as expression host, membrane protein origin, expression vector, fusion-tags, encapsulation reagent and solvent composition are screened in parallel. In this way, constructs with divergent requirements can be produced for a variety of structural applications. As structural techniques advance, sample requirements will change. Single-particle cryo-electron microscopy requires less protein than crystallography and as cryo-electron tomography and time-resolved serial crystallography are developed new sample production requirements will evolve. Here we discuss different methods used for the high-throughput production of membrane proteins for structural biology.
Topics: Cryoelectron Microscopy; Crystallography; Humans; Membrane Proteins; Molecular Biology
PubMed: 34623416
DOI: 10.1042/ETLS20210196 -
Science China. Life Sciences Jan 2015Membrane proteins are involved in various critical biological processes, and studying membrane proteins represents a major challenge in protein biochemistry. As shown by... (Review)
Review
Membrane proteins are involved in various critical biological processes, and studying membrane proteins represents a major challenge in protein biochemistry. As shown by both structural and functional studies, the membrane environment plays an essential role for membrane proteins. In vitro studies are reliant on the successful reconstitution of membrane proteins. This review describes the interaction between detergents and lipids that aids the understanding of the reconstitution processes. Then the techniques of detergent removal and a few useful techniques to refine the formed proteoliposomes are reviewed. Finally the applications of reconstitution techniques to study membrane proteins involved in Ca(2+) signaling are summarized.
Topics: Detergents; In Vitro Techniques; Membrane Proteins; Microscopy, Electron; Structure-Activity Relationship
PubMed: 25576454
DOI: 10.1007/s11427-014-4769-0 -
Protein Science : a Publication of the... Dec 2020The question of how proteins manage to organize into a unique three-dimensional structure has been a major field of study since the first protein structures were... (Review)
Review
The question of how proteins manage to organize into a unique three-dimensional structure has been a major field of study since the first protein structures were determined. For membrane proteins, the question is made more complex because, unlike water-soluble proteins, the solvent is not homogenous or even unique. Each cell and organelle has a distinct lipid composition that can change in response to environmental stimuli. Thus, the study of membrane protein folding requires not only understanding how the unfolded chain navigates its way to the folded state, but also how changes in bilayer properties can affect that search. Here we review what we know so far about the impact of lipid composition on bilayer physical properties and how those properties can affect folding. A better understanding of the lipid bilayer and its effects on membrane protein folding is not only important for a theoretical understanding of the folding process, but can also have a practical impact on our ability to work with and design membrane proteins.
Topics: Cell Membrane; Lipid Bilayers; Membrane Proteins; Models, Molecular; Protein Folding; Protein Structure, Secondary
PubMed: 33058341
DOI: 10.1002/pro.3973