| Role of Bundle Helices in a Regulatory Crosstalk in the Trimeric Betaine Transporter BetP. | |
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MedLine Citation:
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PMID: 22024596 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The Na(+)-coupled betaine symporter BetP regulates transport activity in response to hyperosmotic stress only in its trimeric state, suggesting a regulatory crosstalk between individual protomers. BetP shares the overall fold of two inverted structurally related five-transmembrane (TM) helix repeats with the sequence-unrelated Na(+)-coupled symporters LeuT, vSGLT, and Mhp1, which are neither trimeric nor regulated in transport activity. Conformational changes characteristic for this transporter fold involve the two first helices of each repeat, which form a four-TM-helix bundle. Here, we identify two ionic networks in BetP located on both sides of the membrane that might be responsible for BetP's unique regulatory behavior by restricting the conformational flexibility of the four-TM-helix bundle. The cytoplasmic ionic interaction network links both first helices of each repeat in one protomer to the osmosensing C-terminal domain of the adjacent protomer. Moreover, the periplasmic ionic interaction network conformationally locks the four-TM-helix bundle between the same neighbor protomers. By a combination of site-directed mutagenesis, cross-linking, and betaine uptake measurements, we demonstrate how conformational changes in individual bundle helices are transduced to the entire bundle by specific inter-helical interactions. We suggest that one purpose of bundle networking is to assist crosstalk between protomers during transport regulation by specifically modulating the transition from outward-facing to inward-facing state. |
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Authors:
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Rebecca M Gärtner; Camilo Perez; Caroline Koshy; Christine Ziegler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-15 |
Journal Detail:
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Title: Journal of molecular biology Volume: - ISSN: 1089-8638 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985088R Medline TA: J Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ltd. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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