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 m...

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Main Authors: Joanna eLee, Zara eSands, Philip eBiggin
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-06-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmolb.2016.00021/full
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author Joanna eLee
Zara eSands
Philip eBiggin
author_facet Joanna eLee
Zara eSands
Philip eBiggin
author_sort Joanna eLee
collection DOAJ
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 modelling 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 analysed 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 modelling 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 twelve transmembrane regions.
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spelling doaj.art-f9194bf725184011b47e641884539b1b2022-12-21T20:37:10ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2016-06-01310.3389/fmolb.2016.00021187476A Numbering System for MFS Transporter ProteinsJoanna eLee0Zara eSands1Philip eBiggin2University of OxfordUCB Pharma S.A.University of OxfordThe 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 modelling 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 analysed 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 modelling 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 twelve transmembrane regions.http://journal.frontiersin.org/Journal/10.3389/fmolb.2016.00021/fulltransportHomology modellinglacYalternating accesstransmembrane.
spellingShingle Joanna eLee
Zara eSands
Philip eBiggin
A Numbering System for MFS Transporter Proteins
Frontiers in Molecular Biosciences
transport
Homology modelling
lacY
alternating access
transmembrane.
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 transport
Homology modelling
lacY
alternating access
transmembrane.
url http://journal.frontiersin.org/Journal/10.3389/fmolb.2016.00021/full
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AT zaraesands numberingsystemformfstransporterproteins
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