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Dynamic protein ligand interactions – insights from MS

Proteins undergo dynamic interactions with carbohydrates, lipids and nucleotides to form catalytic cores, fine‐tuned for different cellular actions. The study of dynamic interactions between proteins and their cognate ligands is therefore fundamental to the understanding of biological systems. Durin...

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Detalles Bibliográficos
Autores principales: Schmidt, Carla, Robinson, Carol V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154455/
https://www.ncbi.nlm.nih.gov/pubmed/24393119
http://dx.doi.org/10.1111/febs.12707
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author Schmidt, Carla
Robinson, Carol V.
author_facet Schmidt, Carla
Robinson, Carol V.
author_sort Schmidt, Carla
collection PubMed
description Proteins undergo dynamic interactions with carbohydrates, lipids and nucleotides to form catalytic cores, fine‐tuned for different cellular actions. The study of dynamic interactions between proteins and their cognate ligands is therefore fundamental to the understanding of biological systems. During the last two decades MS, and its associated techniques, has become accepted as a method for the study of protein–ligand interactions, not only for covalent complexes, where the use of MS is well established, but also, and significantly for protein–ligand interactions, for noncovalent assemblies. In this review, we employ a broad definition of a ligand to encompass protein subunits, drug molecules, oligonucleotides, carbohydrates, and lipids. Under the appropriate conditions, MS can reveal the composition, heterogeneity and dynamics of these protein–ligand interactions, and in some cases their structural arrangements and binding affinities. Herein, we highlight MS approaches for studying protein–ligand complexes, including those containing integral membrane subunits, and showcase examples from recent literature. Specifically, we tabulate the myriad of methodologies, including hydrogen exchange, proteomics, hydroxyl radical footprinting, intact complexes, and crosslinking, which, when combined with MS, provide insights into conformational changes and subtle modifications in response to ligand‐binding interactions.
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spelling pubmed-41544552014-09-22 Dynamic protein ligand interactions – insights from MS Schmidt, Carla Robinson, Carol V. FEBS J Minireviews Proteins undergo dynamic interactions with carbohydrates, lipids and nucleotides to form catalytic cores, fine‐tuned for different cellular actions. The study of dynamic interactions between proteins and their cognate ligands is therefore fundamental to the understanding of biological systems. During the last two decades MS, and its associated techniques, has become accepted as a method for the study of protein–ligand interactions, not only for covalent complexes, where the use of MS is well established, but also, and significantly for protein–ligand interactions, for noncovalent assemblies. In this review, we employ a broad definition of a ligand to encompass protein subunits, drug molecules, oligonucleotides, carbohydrates, and lipids. Under the appropriate conditions, MS can reveal the composition, heterogeneity and dynamics of these protein–ligand interactions, and in some cases their structural arrangements and binding affinities. Herein, we highlight MS approaches for studying protein–ligand complexes, including those containing integral membrane subunits, and showcase examples from recent literature. Specifically, we tabulate the myriad of methodologies, including hydrogen exchange, proteomics, hydroxyl radical footprinting, intact complexes, and crosslinking, which, when combined with MS, provide insights into conformational changes and subtle modifications in response to ligand‐binding interactions. Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies 2014-01-21 2014-04 /pmc/articles/PMC4154455/ /pubmed/24393119 http://dx.doi.org/10.1111/febs.12707 Text en © 2014 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/3.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Minireviews
Schmidt, Carla
Robinson, Carol V.
Dynamic protein ligand interactions – insights from MS
title Dynamic protein ligand interactions – insights from MS
title_full Dynamic protein ligand interactions – insights from MS
title_fullStr Dynamic protein ligand interactions – insights from MS
title_full_unstemmed Dynamic protein ligand interactions – insights from MS
title_short Dynamic protein ligand interactions – insights from MS
title_sort dynamic protein ligand interactions – insights from ms
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154455/
https://www.ncbi.nlm.nih.gov/pubmed/24393119
http://dx.doi.org/10.1111/febs.12707
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