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A Numbering System for MFS Transporter Proteins

The Major Facilitator Superfamily (MFS) is one of the largest classes of secondary active transporters and is widely expressed in many domains of life. It is characterized by a common 12-transmembrane helix motif that allows the selective transport of a vast range of diverse substrates across the me...

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Autores principales: Lee, Joanna, Sands, Zara A., Biggin, Philip C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889909/
https://www.ncbi.nlm.nih.gov/pubmed/27314000
http://dx.doi.org/10.3389/fmolb.2016.00021
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author Lee, Joanna
Sands, Zara A.
Biggin, Philip C.
author_facet Lee, Joanna
Sands, Zara A.
Biggin, Philip C.
author_sort Lee, Joanna
collection PubMed
description The Major Facilitator Superfamily (MFS) is one of the largest classes of secondary active transporters and is widely expressed in many domains of life. It is characterized by a common 12-transmembrane helix motif that allows the selective transport of a vast range of diverse substrates across the membrane. MFS transporters play a central role in many physiological processes and are increasingly recognized as potential drug targets. Despite intensive efforts, there are still only a handful of crystal structures and therefore homology modeling is likely to be a necessary process for providing models to interpret experiments for many years to come. However, the diversity of sequences and the multiple conformational states these proteins can exist in makes the process significantly more complicated, especially for sequences for which there is very little sequence identity to known templates. Inspired by the approach adopted many years ago for GPCRs, we have analyzed the large number of MFS sequences now available alongside the current structural information to propose a series of conserved contact points that can provide additional guidance for the homology modeling process. To enable cross-comparison across MFS models we also present a numbering scheme that can be used to provide a point of reference within each of the 12 transmembrane regions.
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spelling pubmed-48899092016-06-16 A Numbering System for MFS Transporter Proteins Lee, Joanna Sands, Zara A. Biggin, Philip C. Front Mol Biosci Molecular Biosciences The Major Facilitator Superfamily (MFS) is one of the largest classes of secondary active transporters and is widely expressed in many domains of life. It is characterized by a common 12-transmembrane helix motif that allows the selective transport of a vast range of diverse substrates across the membrane. MFS transporters play a central role in many physiological processes and are increasingly recognized as potential drug targets. Despite intensive efforts, there are still only a handful of crystal structures and therefore homology modeling is likely to be a necessary process for providing models to interpret experiments for many years to come. However, the diversity of sequences and the multiple conformational states these proteins can exist in makes the process significantly more complicated, especially for sequences for which there is very little sequence identity to known templates. Inspired by the approach adopted many years ago for GPCRs, we have analyzed the large number of MFS sequences now available alongside the current structural information to propose a series of conserved contact points that can provide additional guidance for the homology modeling process. To enable cross-comparison across MFS models we also present a numbering scheme that can be used to provide a point of reference within each of the 12 transmembrane regions. Frontiers Media S.A. 2016-06-02 /pmc/articles/PMC4889909/ /pubmed/27314000 http://dx.doi.org/10.3389/fmolb.2016.00021 Text en Copyright © 2016 Lee, Sands and Biggin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Lee, Joanna
Sands, Zara A.
Biggin, Philip C.
A Numbering System for MFS Transporter Proteins
title A Numbering System for MFS Transporter Proteins
title_full A Numbering System for MFS Transporter Proteins
title_fullStr A Numbering System for MFS Transporter Proteins
title_full_unstemmed A Numbering System for MFS Transporter Proteins
title_short A Numbering System for MFS Transporter Proteins
title_sort numbering system for mfs transporter proteins
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889909/
https://www.ncbi.nlm.nih.gov/pubmed/27314000
http://dx.doi.org/10.3389/fmolb.2016.00021
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