4m8j | pdb_00004m8j

Crystal structure of CaiT R262E bound to gamma-butyrobetaine

spinqualitylabelsall models 4m8j, resolution 3.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4m8j is a 1 chain structure with sequence from Proteus mirabilis ATCC 29906. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.294Å Ligands: NM2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CAIT_PROMH Catalyzes the exchange of L-carnitine for gamma-butyrobetaine.[HAMAP-Rule:MF_01049] Publication Abstract from PubMed Most secondary-active transporters transport their substrates using an electrochemical ion gradient. In contrast, the carnitine transporter (CaiT) is an ion-independent, l-carnitine/gamma-butyrobetaine antiporter belonging to the betaine/carnitine/choline transporter family of secondary transporters. Recently determined crystal structures of CaiT from Escherichia coli and Proteus mirabilis revealed an inverted five-transmembrane-helix repeat similar to that in the amino acid/Na+ symporter LeuT. The ion independence of CaiT makes it unique in this family. Here we show that mutations of arginine 262 (R262) make CaiT Na+-dependent. The transport activity of R262 mutants increased by 30-40% in the presence of a membrane potential, indicating substrate/Na+ cotransport. Structural and biochemical characterization revealed that R262 plays a crucial role in substrate binding by stabilizing the partly unwound TM1' helix. Modeling CaiT from P. mirabilis in the outward-open and closed states on the corresponding structures of the related symporter BetP reveals alternating orientations of the buried R262 sidechain, which mimic sodium binding and unbinding in the Na+-coupled substrate symporters. We propose that a similar mechanism is operative in other Na+/H+-independent transporters, in which a positively charged amino acid replaces the cotransported cation. The oscillation of the R262 sidechain in CaiT indicates how a positive charge triggers the change between outward-open and inward-open conformations as a unifying critical step in LeuT-type transporters. Arginine oscillation explains Na+ independence in the substrate/product antiporter CaiT.,Kalayil S, Schulze S, Kuhlbrandt W Proc Natl Acad Sci U S A. 2013 Oct 7. PMID:24101465 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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