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Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation

The major facilitator superfamily (MFS) is the largest secondary transporter family and is responsible for transporting a broad range of substrates across the biomembrane. These proteins are involved in a series of conformational changes during substrate transport. To decipher the transport mechanis...

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Autores principales: Xiao, Qingjie, Xu, Mengxue, Wang, Weiwei, Wu, Tingting, Zhang, Weizhe, Qin, Wenming, Sun, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266783/
https://www.ncbi.nlm.nih.gov/pubmed/35806248
http://dx.doi.org/10.3390/ijms23137235
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author Xiao, Qingjie
Xu, Mengxue
Wang, Weiwei
Wu, Tingting
Zhang, Weizhe
Qin, Wenming
Sun, Bo
author_facet Xiao, Qingjie
Xu, Mengxue
Wang, Weiwei
Wu, Tingting
Zhang, Weizhe
Qin, Wenming
Sun, Bo
author_sort Xiao, Qingjie
collection PubMed
description The major facilitator superfamily (MFS) is the largest secondary transporter family and is responsible for transporting a broad range of substrates across the biomembrane. These proteins are involved in a series of conformational changes during substrate transport. To decipher the transport mechanism, it is necessary to obtain structures of these different conformations. At present, great progress has been made in predicting protein structure based on coevolutionary information. In this study, AlphaFold2 was used to predict different conformational structures for 69 MFS transporters of E. coli after the selective mutation of residues at the interface between the N- and C-terminal domains. The predicted structures for these mutants had small RMSD values when compared to structures obtained using X-ray crystallography, which indicates that AlphaFold2 predicts the structure of MSF transporters with high accuracy. In addition, different conformations of other transporter family proteins have been successfully predicted based on mutation methods. This study provides a structural basis to study the transporting mechanism of the MFS transporters and a method to probe dynamic conformation changes of transporter family proteins when performing their function.
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spelling pubmed-92667832022-07-09 Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation Xiao, Qingjie Xu, Mengxue Wang, Weiwei Wu, Tingting Zhang, Weizhe Qin, Wenming Sun, Bo Int J Mol Sci Article The major facilitator superfamily (MFS) is the largest secondary transporter family and is responsible for transporting a broad range of substrates across the biomembrane. These proteins are involved in a series of conformational changes during substrate transport. To decipher the transport mechanism, it is necessary to obtain structures of these different conformations. At present, great progress has been made in predicting protein structure based on coevolutionary information. In this study, AlphaFold2 was used to predict different conformational structures for 69 MFS transporters of E. coli after the selective mutation of residues at the interface between the N- and C-terminal domains. The predicted structures for these mutants had small RMSD values when compared to structures obtained using X-ray crystallography, which indicates that AlphaFold2 predicts the structure of MSF transporters with high accuracy. In addition, different conformations of other transporter family proteins have been successfully predicted based on mutation methods. This study provides a structural basis to study the transporting mechanism of the MFS transporters and a method to probe dynamic conformation changes of transporter family proteins when performing their function. MDPI 2022-06-29 /pmc/articles/PMC9266783/ /pubmed/35806248 http://dx.doi.org/10.3390/ijms23137235 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiao, Qingjie
Xu, Mengxue
Wang, Weiwei
Wu, Tingting
Zhang, Weizhe
Qin, Wenming
Sun, Bo
Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation
title Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation
title_full Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation
title_fullStr Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation
title_full_unstemmed Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation
title_short Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation
title_sort utilization of alphafold2 to predict mfs protein conformations after selective mutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266783/
https://www.ncbi.nlm.nih.gov/pubmed/35806248
http://dx.doi.org/10.3390/ijms23137235
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