Inter-residue interactions in alpha-helical transmembrane proteins

2018 ◽  
Vol 35 (15) ◽  
pp. 2578-2584 ◽  
Author(s):  
Eduardo Mayol ◽  
Mercedes Campillo ◽  
Arnau Cordomí ◽  
Mireia Olivella
Keyword(s):  
Membrane Proteins ◽  
Present Report ◽  
Protein Structures ◽  
Transmembrane Proteins ◽  
Globular Proteins ◽  
Supplementary Information ◽  
Backbone Carbonyl ◽  
Composition Characteristic ◽  
Almost All ◽  
Residue Composition

Abstract Motivation The number of available membrane protein structures has markedly increased in the last years and, in parallel, the reliability of the methods to detect transmembrane (TM) segments. In the present report, we characterized inter-residue interactions in α-helical membrane proteins using a dataset of 3462 TM helices from 430 proteins. This is by far the largest analysis published to date. Results Our analysis of residue–residue interactions in TM segments of membrane proteins shows that almost all interactions involve aliphatic residues and Phe. There is lack of polar–polar, polar–charged and charged–charged interactions except for those between Thr or Ser sidechains and the backbone carbonyl of aliphatic and Phe residues. The results are discussed in the context of the preferences of amino acids to be in the protein core or exposed to the lipid bilayer and to occupy specific positions along the TM segment. Comparison to datasets of β-barrel membrane proteins and of α-helical globular proteins unveils the specific patterns of interactions and residue composition characteristic of α-helical membrane proteins that are the clue to understanding their structure. Availability and implementation Results data and datasets used are available at http://lmc.uab.cat/TMalphaDB/interactions.php. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals BRANEart: identify stability strength and weakness regions in membrane proteins

2021 ◽  
Author(s):  
Sankar Basu ◽  
Simon S. Assaf ◽  
Fabian Teheux ◽  
Marianne Rooman ◽  
Fabrizio Pucci
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Conformational Changes ◽  
Large Scale ◽  
Protein Structures ◽  
Accurate Method ◽  
Globular Proteins ◽  
Stability Properties ◽  
Overall Stability ◽  
The Stability

AbstractUnderstanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contributions to the overall stability of membrane proteins. It is based on an extended set of recently introduced statistical potentials derived from membrane protein structures, which better describe the stability properties of this class of proteins than standard potentials derived from globular proteins. We defined a per-residue membrane propensity index from combinations of these potentials, which can be used to identify residues which strongly contribute to the stability of the transmembrane region or which would, on the contrary, be more stable in extramembrane regions, or vice versa. Large-scale application to membrane and globular proteins sets and application to tests cases show excellent agreement with experimental data. BRANEart thus appears as a useful instrument to analyze in detail the overall stability properties of a target membrane protein, to position it relative to the lipid bilayer, and to rationally modify its biophysical characteristics and function. BRANEart can be freely accessed from http://babylone.3bio.ulb.ac.be/BRANEart.

scholarly journals MemBlob database and server for identifying transmembrane regions using cryo-EM maps

2019 ◽  
Vol 36 (8) ◽  
pp. 2595-2598 ◽  
Author(s):  
Bianka Farkas ◽  
Georgina Csizmadia ◽  
Eszter Katona ◽  
Gábor E Tusnády ◽  
Tamás Hegedűs
Keyword(s):  
Protein Structures ◽  
Transmembrane Proteins ◽  
Bulk Water ◽  
Supplementary Information ◽  
Hydrophobic Core ◽  
Transmembrane Helices ◽  
Cryo Electron Microscopy ◽  
Density Maps ◽  
Transmembrane Regions ◽  
Atomistic Structure

Abstract Summary The identification of transmembrane helices in transmembrane proteins is crucial, not only to understand their mechanism of action but also to develop new therapies. While experimental data on the boundaries of membrane-embedded regions are sparse, this information is present in cryo-electron microscopy (cryo-EM) density maps and it has not been utilized yet for determining membrane regions. We developed a computational pipeline, where the inputs of a cryo-EM map, the corresponding atomistic structure, and the potential bilayer orientation determined by TMDET algorithm of a given protein result in an output defining the residues assigned to the bulk water phase, lipid interface and the lipid hydrophobic core. Based on this method, we built a database involving published cryo-EM protein structures and a server to be able to compute this data for newly obtained structures. Availability and implementation http://memblob.hegelab.org. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals BRANEart: Identify Stability Strength and Weakness Regions in Membrane Proteins

2021 ◽  
Vol 1 ◽  
Author(s):  
Sankar Basu ◽  
Simon S. Assaf ◽  
Fabian Teheux ◽  
Marianne Rooman ◽  
Fabrizio Pucci
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Conformational Changes ◽  
Large Scale ◽  
Protein Structures ◽  
Accurate Method ◽  
Globular Proteins ◽  
Stability Properties ◽  
Overall Stability ◽  
The Stability

Understanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contributions to the overall stability of membrane proteins. It is based on an extended set of recently introduced statistical potentials derived from membrane protein structures, which better describe the stability properties of this class of proteins than standard potentials derived from globular proteins. We defined a per-residue membrane propensity index from combinations of these potentials, which can be used to identify residues which strongly contribute to the stability of the transmembrane region or which would, on the contrary, be more stable in extramembrane regions, or vice versa. Large-scale application to membrane and globular proteins sets and application to tests cases show excellent agreement with experimental data. BRANEart thus appears as a useful instrument to analyze in detail the overall stability properties of a target membrane protein, to position it relative to the lipid bilayer, and to rationally modify its biophysical characteristics and function. BRANEart can be freely accessed from http://babylone.3bio.ulb.ac.be/BRANEart.

scholarly journals The TMCrys server for supporting crystallization of transmembrane proteins

2019 ◽  
Vol 35 (20) ◽  
pp. 4203-4204
Author(s):  
Julia K Varga ◽  
Gábor E Tusnády
Keyword(s):  
Membrane Proteins ◽  
Structure Determination ◽  
Web Server ◽  
Transmembrane Proteins ◽  
Prediction Method ◽  
Supplementary Information ◽  
Supplementary Data ◽  
Successful Completion ◽  
Determination Process

Abstract Motivation Due to their special properties, the structures of transmembrane proteins are extremely hard to determine. Several methods exist to predict the propensity of successful completion of the structure determination process. However, available predictors incorporate data of any kind of proteins, hence they can hardly differentiate between crystallizable and non-crystallizable membrane proteins. Results We implemented a web server to simplify running TMCrys prediction method that was developed specifically to separate crystallizable and non-crystallizable membrane proteins. Availability and implementation http://tmcrys.enzim.ttk.mta.hu Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Computing structure-based lipid accessibility of membrane proteins with mp_lipid_acc in RosettaMP

2016 ◽  
Author(s):  
Julia Koehler Leman ◽  
Sergey Lyskov ◽  
Richard Bonneau
Keyword(s):  
Protein Structure ◽  
Membrane Proteins ◽  
Protein Structures ◽  
Benchmark Dataset ◽  
Solvent Accessible Surface Area ◽  
Supplementary Information ◽  
Essential Property ◽  
Membrane Thickness ◽  
Link Type ◽  
Lipid Accessibility

AbstractBackgroundMembrane proteins are vastly underrepresented in structural databases, which has led to a lack of computational tools and the corresponding inappropriate use of tools designed for soluble proteins. For membrane proteins, lipid accessibility is an essential property. Even though programs are available for sequence-based prediction of lipid accessibility and structure-based identification of solvent-accessible surface area, the latter does not distinguish between water accessible and lipid accessible residues in membrane proteins.ResultsHere we present mp_lipid_acc, the first method to identify lipid accessible residues from the protein structure, implemented in the RosettaMP framework and available as a webserver. Our method uses protein structures transformed in membrane coordinates, for instance from PDBTM or OPM databases, and a defined membrane thickness to classify lipid accessibility of residues. mp_lipid_acc is applicable to both α-helical and β-barrel membrane proteins of diverse architectures with or without water-filled pores and uses a concave hull algorithm for classification. We further provide a manually curated benchmark dataset, on which our method achieves prediction accuracies of 90%.ConclusionWe present a novel tool to classify lipid accessibility from the protein structure, which is applicable to proteins of diverse architectures and achieves prediction accuracies of 90% on a manually curated database. mp_lipid_acc is part of the Rosetta software suite, available at www.rosettacommons.org. The webserver is available at http://rosie.graylab.jhu.edu/mp_lipid_acc/submit and the benchmark dataset is available at http://tinyurl.com/mp-lipid-acc-dataset.Supplementary informationSupplementary information is available at BMC Bioinformatics.

scholarly journals On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures

2016 ◽  
Vol 25 (4) ◽  
pp. 887-897 ◽  
Author(s):  
Gail J. Bartlett ◽  
Derek N. Woolfson
Keyword(s):  
Protein Structures ◽  
Backbone Carbonyl ◽  
Lone Pairs

scholarly journals Expression of 3 beta-hydroxysteroid dehydrogenase/isomerase in the female rat pituitary

2000 ◽  
Vol 166 (1) ◽  
pp. 95-101 ◽  
Author(s):  
S Vidal ◽  
A Roman ◽  
L Moya ◽  
K Kovacs
Keyword(s):  
Present Report ◽  
Hydroxysteroid Dehydrogenase ◽  
Anterior Lobe ◽  
Female Rats ◽  
Endocrine Function ◽  
Pars Intermedia ◽  
Posterior Lobe ◽  
Female Rat ◽  
Target Organs ◽  
Almost All

3 beta-Hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) catalyses an essential step in the biosynthesis of steroid hormones and is widely distributed in peripheral steroid target organs. The present report describes for first time the expression of this enzyme in the pituitary of female rats. Immunohistochemistry at the light microscopic level was performed on pro-oestrous and ovariectomized rat pituitaries. Immunoreactive cells were scattered and randomly distributed throughout the anterior lobe, whereas cells located in the posterior lobe and pars intermedia were immunonegative. Differences were observed in cell morphology and in the number of 3 beta-HSD-immunopositive cells between ovariectomized and pro-oestrous female rat pituitaries, suggesting that steroidogenic activity is affected by ovarian endocrine function. Apart from adenohypophyseal immunoreactive cells, 3 beta-HSD immunopositivity was also noted in endothelial cells of almost all pituitary capillaries located in the anterior and posterior lobes.

A Solid-State NMR Approach to Structure Determination of Membrane-Associated Peptides and Proteins

1997 ◽  
Author(s):  
S.J. Opella ◽  
L.E. Chirlian
Keyword(s):  
Nmr Spectroscopy ◽  
Membrane Proteins ◽  
Structural Biology ◽  
Experimental Studies ◽  
Globular Proteins ◽  
Biological Properties ◽  
Cellular Functions ◽  
X Ray ◽  
X Ray Crystallography ◽  
Form And Function

Structural biology relies on detailed descriptions of the three-dimensional structures of peptides, proteins, and other biopolymers to explain the form and function of biological systems ranging in complexity from individual molecules to entire organisms. NMR spectroscopy and X-ray crystallography, in combination with several types of calculations, provide the required structural information. In recent years, the structures of several hundred proteins have been determined by one or both of these experimental methods. However, since the protein molecules must either reorient rapidly in samples for multidimensional solution NMR spectroscopy or form high quality single crystals in samples for X-ray crystallography, nearly all of the structures determined up to now have been of the soluble, globular proteins that are found in the cytoplasm and periplasmof cells and fortuitously have these favorable properties. Since only a minority of biological properties are expressed by globular proteins, and proteins, in general, have evolved in order to express specific functions rather than act as samples for experimental studies, there are other classes of proteins whose structures are currently unknown but are of keen interest in structural biology. More than half of all proteins appear to be associated with membranes, and many cellular functions are expressed by proteins in other types of supramolecular complexes with nucleic acids, carbohydrates, or other proteins. The interest in the structures of membrane proteins, structural proteins, and proteins in complexes provides many opportunities for the further development and application of NMR spectroscopy. Our understanding of polypeptides associated with lipids in membranes, in particular, is primitive, especially compared to that for globular proteins. This is largely a consequence of the experimental difficulties encountered in their study by conventional NMR and X-ray approaches. Fortunately, the principal features of two major classes of membrane proteins have been identified from studies of several tractable examples. Bacteriorhodopsin (Henderson et al., 1990), the subunits of the photosynthetic reaction center (Deisenhofer et al., 1985), and filamentous bacteriophage coat proteins (Shon et al., 1991; McDonnell et al., 1993) have all been shown to have long transmembrane hydrophobic helices, shorter amphipathic bridging helices in the plane of the bilayers, both structured and mobile loops connecting the helices, and mobile N- and C-terminal regions.

Mutations in transmembrane proteins: diseases, evolutionary insights, prediction and comparison with globular proteins

2020 ◽  
Author(s):  
Jan Zaucha ◽  
Michael Heinzinger ◽  
A Kulandaisamy ◽  
Evans Kataka ◽  
Óscar Llorian Salvádor ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Lipid Bilayers ◽  
Protein Structures ◽  
Experimental Studies ◽  
Single Amino Acid ◽  
Evolutionary Information ◽  
Missense Variants ◽  
Current State ◽  
Aqueous Environments

Abstract Membrane proteins are unique in that they interact with lipid bilayers, making them indispensable for transporting molecules and relaying signals between and across cells. Due to the significance of the protein’s functions, mutations often have profound effects on the fitness of the host. This is apparent both from experimental studies, which implicated numerous missense variants in diseases, as well as from evolutionary signals that allow elucidating the physicochemical constraints that intermembrane and aqueous environments bring. In this review, we report on the current state of knowledge acquired on missense variants (referred to as to single amino acid variants) affecting membrane proteins as well as the insights that can be extrapolated from data already available. This includes an overview of the annotations for membrane protein variants that have been collated within databases dedicated to the topic, bioinformatics approaches that leverage evolutionary information in order to shed light on previously uncharacterized membrane protein structures or interaction interfaces, tools for predicting the effects of mutations tailored specifically towards the characteristics of membrane proteins as well as two clinically relevant case studies explaining the implications of mutated membrane proteins in cancer and cardiomyopathy.

scholarly journals DiscoRhythm: an easy-to-use web application and R package for discovering rhythmicity

2019 ◽  
Author(s):  
Matthew Carlucci ◽  
Algimantas Kriščiūnas ◽  
Haohan Li ◽  
Povilas Gibas ◽  
Karolis Koncevičius ◽  
...  
Keyword(s):  
Web Application ◽  
Statistical Significance ◽  
R Package ◽  
Biological Data ◽  
Supplementary Information ◽  
Statistical Knowledge ◽  
Health And Disease ◽  
Phase Amplitude ◽  
Almost All ◽  
User Friendly

Abstract Motivation Biological rhythmicity is fundamental to almost all organisms on Earth and plays a key role in health and disease. Identification of oscillating signals could lead to novel biological insights, yet its investigation is impeded by the extensive computational and statistical knowledge required to perform such analysis. Results To address this issue, we present DiscoRhythm (Discovering Rhythmicity), a user-friendly application for characterizing rhythmicity in temporal biological data. DiscoRhythm is available as a web application or an R/Bioconductor package for estimating phase, amplitude, and statistical significance using four popular approaches to rhythm detection (Cosinor, JTK Cycle, ARSER, and Lomb-Scargle). We optimized these algorithms for speed, improving their execution times up to 30-fold to enable rapid analysis of -omic-scale datasets in real-time. Informative visualizations, interactive modules for quality control, dimensionality reduction, periodicity profiling, and incorporation of experimental replicates make DiscoRhythm a thorough toolkit for analyzing rhythmicity. Availability and Implementation The DiscoRhythm R package is available on Bioconductor (https://bioconductor.org/packages/DiscoRhythm), with source code available on GitHub (https://github.com/matthewcarlucci/DiscoRhythm) under a GPL-3 license. The web application is securely deployed over HTTPS (https://disco.camh.ca) and is freely available for use worldwide. Local instances of the DiscoRhythm web application can be created using the R package or by deploying the publicly available Docker container (https://hub.docker.com/r/mcarlucci/discorhythm). Supplementary information Supplementary data are available at Bioinformatics online.

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