View source for 7nf8


==Ovine (b0,+AT-rBAT)2 hetero-tetramer, asymmetric unit, rigid-body fitted==
<StructureSection load='7nf8' size='340' side='right'caption='[[7nf8]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nf8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NF8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NF8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.83&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=LBN:(2R)-3-(hexadecanoyloxy)-2-{[(9Z)-octadec-9-enoyl]oxy}propyl+2-(trimethylazaniumyl)ethyl+phosphate'>LBN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7nf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nf8 OCA], [https://pdbe.org/7nf8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nf8 RCSB], [https://www.ebi.ac.uk/pdbsum/7nf8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nf8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A6P3EL78_SHEEP A0A6P3EL78_SHEEP] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cystinuria is a genetic disorder characterized by overexcretion of dibasic amino acids and cystine, causing recurrent kidney stones and kidney failure. Mutations of the regulatory glycoprotein rBAT and the amino acid transporter b(0,+)AT, which constitute system b(0,+), are linked to type I and non-type I cystinuria respectively and they exhibit distinct phenotypes due to protein trafficking defects or catalytic inactivation. Here, using electron cryo-microscopy and biochemistry, we discover that Ca(2+) mediates higher-order assembly of system b(0,+). Ca(2+) stabilizes the interface between two rBAT molecules, leading to super-dimerization of b(0,+)AT-rBAT, which in turn facilitates N-glycan maturation and protein trafficking. A cystinuria mutant T216M and mutations of the Ca(2+) site of rBAT cause the loss of higher-order assemblies, resulting in protein trapping at the ER and the loss of function. These results provide the molecular basis of system b(0,+) biogenesis and type I cystinuria and serve as a guide to develop new therapeutic strategies against it. More broadly, our findings reveal an unprecedented link between transporter oligomeric assembly and protein-trafficking diseases.

Ca(2+)-mediated higher-order assembly of heterodimers in amino acid transport system b(0,+) biogenesis and cystinuria.,Lee Y, Wiriyasermkul P, Kongpracha P, Moriyama S, Mills DJ, Kuhlbrandt W, Nagamori S Nat Commun. 2022 May 16;13(1):2708. doi: 10.1038/s41467-022-30293-9. PMID:35577790<ref>PMID:35577790</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nf8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Ovis aries]]
[[Category: Kuehlbrandt W]]
[[Category: Lee Y]]