2wit

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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The trimeric Na(+)-coupled betaine symporter BetP from Corynebactrium glutamicum adjusts transport activity according to the external osmolality. BetP senses the increasing internal K(+) concentration, which is an immediate consequence of osmotic upshift in C. glutamicum. It is assumed that BetP specifically binds potassium to yet unidentified binding sites, thereby inducing conformational changes resulting in activation. Atomic structures of BetP were obtained in the absence of potassium allowing only a speculative glimpse on a putative mechanism of K(+)-induced transport activation. The structural data suggest that activation in BetP is crucially linked to its trimeric state involving an interaction network between several arginines and glutamates and aspartates. Here, we describe the effect of K(+)-induced activation on the specific ionic interaction sites in terminal domains and loops and on the protomer-protomer interactions within the trimer studied by ATR-FTIR spectroscopy. We suggest that arginine and aspartate and/or glutamate residues at the trimeric interface rearrange upon K(+)-induced activation, although they remain assembled in an interaction network. Our data propose a two-step mechanism comprising first a change in solvent exposure of charged residues and second a modification of their interaction sites in a partner-switching manner. FTIR reveals a higher alpha-helical content than expected from the X-ray structures that we attribute to the structurally unresolved N-terminal domain modulating regulation. In situ (1)H/(2)H exchange studies point toward an altered exposure of backbone regions to buffer solution upon activation, most likely due to conformational changes in both terminal domains, which further affects ionic interactions within the trimer.
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Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by accumulation of osmolytes to restore normal hydration levels. Here we report the determination of the X-ray structure of a member of the family of betaine/choline/carnitine transporters, the Na(+)-coupled symporter BetP from Corynebacterium glutamicum, which is a highly effective osmoregulated uptake system for glycine betaine. Glycine betaine is bound in a tryptophan box occluded from both sides of the membrane with aromatic side chains lining the transport pathway. BetP has the same overall fold as three unrelated Na(+)-coupled symporters. Whereas these are crystallized in either the outward-facing or the inward-facing conformation, the BetP structure reveals a unique intermediate conformation in the Na(+)-coupled transport cycle. The trimeric architecture of BetP and the break in three-fold symmetry by the osmosensing C-terminal helices suggest a regulatory mechanism of Na(+)-coupled osmolyte transport to counteract osmotic stress.
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K(+)-induced conformational changes in the trimeric betaine transporter BetP monitored by ATR-FTIR spectroscopy.,Korkmaz F, Ressl S, Ziegler C, Mantele W Biochim Biophys Acta. 2013 Jan 11. pii: S0005-2736(13)00008-4. doi:, 10.1016/j.bbamem.2013.01.004. PMID:23318153<ref>PMID:23318153</ref>
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Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP.,Ressl S, Terwisscha van Scheltinga AC, Vonrhein C, Ott V, Ziegler C Nature. 2009 Mar 5;458(7234):47-52. PMID:19262666<ref>PMID:19262666</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 06:17, 13 May 2015

CRYSTAL STRUCTURE OF THE SODIUM-COUPLED GLYCINE BETAINE SYMPORTER BETP FROM CORYNEBACTERIUM GLUTAMICUM WITH BOUND SUBSTRATE

2wit, resolution 3.35Å

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