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Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions

Membrane protein oligomerization mediates a wide range of biological events including signal transduction, viral infection and membrane curvature induction. However, the relative contributions of protein-protein and protein-membrane interactions to protein oligomerization remain poorly understood. H...

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Autores principales: Tao, Meixin, Isas, J. Mario, Langen, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093510/
https://www.ncbi.nlm.nih.gov/pubmed/32210350
http://dx.doi.org/10.1038/s41598-020-62343-x
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author Tao, Meixin
Isas, J. Mario
Langen, Ralf
author_facet Tao, Meixin
Isas, J. Mario
Langen, Ralf
author_sort Tao, Meixin
collection PubMed
description Membrane protein oligomerization mediates a wide range of biological events including signal transduction, viral infection and membrane curvature induction. However, the relative contributions of protein-protein and protein-membrane interactions to protein oligomerization remain poorly understood. Here, we used the Ca(2+)-dependent membrane-binding protein ANXB12 as a model system to determine the relative contributions of protein-protein and protein-membrane interactions toward trimer formation. Using an EPR-based detection method, we find that some protein-protein interactions are essential for trimer formation. Surprisingly, these interactions are largely hydrophobic, and they do not include the previously identified salt bridges, which are less important. Interfering with membrane interaction by mutating selected Ca(2+)-ligands or by introducing Lys residues in the membrane-binding loops had variable, strongly position-dependent effects on trimer formation. The strongest effect was observed for the E226Q/E105Q mutant, which almost fully abolished trimer formation without preventing membrane interaction. These results indicate that lipids engage in specific, trimer-stabilizing interactions that go beyond simply providing a concentration-enhancing surface. The finding that protein-membrane interactions are just as important as protein-protein interactions in ANXB12 trimer formation raises the possibility that the formation of specific lipid contacts could be a more widely used driving force for membrane-mediated oligomerization of proteins in general.
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spelling pubmed-70935102020-03-27 Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions Tao, Meixin Isas, J. Mario Langen, Ralf Sci Rep Article Membrane protein oligomerization mediates a wide range of biological events including signal transduction, viral infection and membrane curvature induction. However, the relative contributions of protein-protein and protein-membrane interactions to protein oligomerization remain poorly understood. Here, we used the Ca(2+)-dependent membrane-binding protein ANXB12 as a model system to determine the relative contributions of protein-protein and protein-membrane interactions toward trimer formation. Using an EPR-based detection method, we find that some protein-protein interactions are essential for trimer formation. Surprisingly, these interactions are largely hydrophobic, and they do not include the previously identified salt bridges, which are less important. Interfering with membrane interaction by mutating selected Ca(2+)-ligands or by introducing Lys residues in the membrane-binding loops had variable, strongly position-dependent effects on trimer formation. The strongest effect was observed for the E226Q/E105Q mutant, which almost fully abolished trimer formation without preventing membrane interaction. These results indicate that lipids engage in specific, trimer-stabilizing interactions that go beyond simply providing a concentration-enhancing surface. The finding that protein-membrane interactions are just as important as protein-protein interactions in ANXB12 trimer formation raises the possibility that the formation of specific lipid contacts could be a more widely used driving force for membrane-mediated oligomerization of proteins in general. Nature Publishing Group UK 2020-03-24 /pmc/articles/PMC7093510/ /pubmed/32210350 http://dx.doi.org/10.1038/s41598-020-62343-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tao, Meixin
Isas, J. Mario
Langen, Ralf
Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions
title Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions
title_full Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions
title_fullStr Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions
title_full_unstemmed Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions
title_short Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions
title_sort annexin b12 trimer formation is governed by a network of protein-protein and protein-lipid interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093510/
https://www.ncbi.nlm.nih.gov/pubmed/32210350
http://dx.doi.org/10.1038/s41598-020-62343-x
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