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==Crystal structure of a cysteine-pair mutant (Y113C-P190C) of a bacterial bile acid transporter before disulfide bond formation== | ==Crystal structure of a cysteine-pair mutant (Y113C-P190C) of a bacterial bile acid transporter before disulfide bond formation== | ||
<StructureSection load='7cyg' size='340' side='right'caption='[[7cyg]]' scene=''> | <StructureSection load='7cyg' size='340' side='right'caption='[[7cyg]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CYG OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[7cyg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Yersinia_frederiksenii Yersinia frederiksenii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CYG FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.198Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7cyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cyg OCA], [https://pdbe.org/7cyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cyg RCSB], [https://www.ebi.ac.uk/pdbsum/7cyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cyg ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A380PV03_YERFR A0A380PV03_YERFR] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Apical sodium-dependent bile acid transporter (ASBT) mediates the uptake of bile acids from the ileum lumen into enterocytes and presents a potential target for the treatment of several metabolic diseases, including type 2 diabetes. It has been proposed that the underlying mechanism for transport by ASBT is an elevator-style alternating-access model, which was deduced mainly by comparing high-resolution structures of two bacterial ASBT homologs (ASBTNM from Neisseria meningitides and ASBTYf from Yersinia frederiksenii) in different conformations. However, one important issue is that the only outward-facing structure (PDB entry 4n7x) was obtained with an Na(+)-binding site mutant of ASBTYf, which severely cripples its transport function, and therefore the physiological relevance of the conformation in PDB entry 4n7x requires further careful evaluation. Here, another crystal structure is reported of ASBTYf that was captured in a state closely resembling the conformation in PDB entry 4n7x using an engineered disulfide bridge. The introduced cysteine mutations avoided any proposed Na(+)- or substrate-binding residues, and the resulting mutant retained both structural and functional integrity and behaved similarly to wild-type ASBTYf. These data support the hypothesis that the PDB entry 4n7x-like structure represents a functional outward-facing conformation of ASBTYf in its transport cycle. | |||
An engineered disulfide bridge traps and validates an outward-facing conformation in a bile acid transporter.,Wang X, Lyu Y, Ji Y, Sun Z, Zhou X Acta Crystallogr D Struct Biol. 2021 Jan 1;77(Pt 1):108-116. doi:, 10.1107/S205979832001517X. Epub 2021 Jan 1. PMID:33404530<ref>PMID:33404530</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7cyg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Symporter 3D structures|Symporter 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Yersinia frederiksenii]] | |||
[[Category: Ji Y]] | [[Category: Ji Y]] | ||
[[Category: Lyu Y]] | [[Category: Lyu Y]] | ||
Latest revision as of 19:20, 29 November 2023
Crystal structure of a cysteine-pair mutant (Y113C-P190C) of a bacterial bile acid transporter before disulfide bond formationCrystal structure of a cysteine-pair mutant (Y113C-P190C) of a bacterial bile acid transporter before disulfide bond formation
Structural highlights
FunctionPublication Abstract from PubMedApical sodium-dependent bile acid transporter (ASBT) mediates the uptake of bile acids from the ileum lumen into enterocytes and presents a potential target for the treatment of several metabolic diseases, including type 2 diabetes. It has been proposed that the underlying mechanism for transport by ASBT is an elevator-style alternating-access model, which was deduced mainly by comparing high-resolution structures of two bacterial ASBT homologs (ASBTNM from Neisseria meningitides and ASBTYf from Yersinia frederiksenii) in different conformations. However, one important issue is that the only outward-facing structure (PDB entry 4n7x) was obtained with an Na(+)-binding site mutant of ASBTYf, which severely cripples its transport function, and therefore the physiological relevance of the conformation in PDB entry 4n7x requires further careful evaluation. Here, another crystal structure is reported of ASBTYf that was captured in a state closely resembling the conformation in PDB entry 4n7x using an engineered disulfide bridge. The introduced cysteine mutations avoided any proposed Na(+)- or substrate-binding residues, and the resulting mutant retained both structural and functional integrity and behaved similarly to wild-type ASBTYf. These data support the hypothesis that the PDB entry 4n7x-like structure represents a functional outward-facing conformation of ASBTYf in its transport cycle. An engineered disulfide bridge traps and validates an outward-facing conformation in a bile acid transporter.,Wang X, Lyu Y, Ji Y, Sun Z, Zhou X Acta Crystallogr D Struct Biol. 2021 Jan 1;77(Pt 1):108-116. doi:, 10.1107/S205979832001517X. Epub 2021 Jan 1. PMID:33404530[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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