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==Crystal structure of Trx-like and NHL repeat containing domains of human NHLRC2==
<StructureSection load='6gc1' size='340' side='right'caption='[[6gc1]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gc1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GC1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GC1 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6g7w|6g7w]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NHLRC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gc1 OCA], [http://pdbe.org/6gc1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gc1 RCSB], [http://www.ebi.ac.uk/pdbsum/6gc1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gc1 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
NHLRC2 (NHL repeat-containing protein 2) is an essential protein. Mutations of NHLRC2, including Asp148Tyr, have been recently associated with a novel FINCA disease (fibrosis, neurodegeneration, cerebral angiomatosis), which is fatal in early childhood. To gain insight into the mechanisms of action of this essential protein, we determined the crystal structure of the Trx-like and NHL repeat beta-propeller domains of human NHLRC2 to a resolution of 2.7 A. The structure reveals two domains adjacent to each other that form a cleft containing a conserved CCINC motif. A SAXS structure of full-length NHLRC2 reveals that the non-conserved C-terminal domain does not pack against the N-terminal domains. Analysis of the surface properties of the protein identifies an extended negative electrostatic potential in the surface of the cleft formed by the two domains, which likely forms a binding site for a ligand or interaction partner(s). Bioinformatics analysis discovers homologs across a range of eukaryotic and prokaryotic species and conserved residues map mostly to the adjacent surfaces of the Trx-like and beta-propeller domains that form the cleft, suggesting both that this forms the potential functional site of NHLRC2 and that the function is conserved across species. Asp148 is located in the Trx-like domain and is not conserved across species. The Asp148Tyr mutation destabilizes the structure of the protein by 2 degrees C. The NHLRC2 structure, the first of any of its homologs, provides an important step towards more focused structure-function studies of this essential protein.

Structural analysis of human NHLRC2, mutations of which are associated with FINCA disease.,Biterova E, Ignatyev A, Uusimaa J, Hinttala R, Ruddock LW PLoS One. 2018 Aug 23;13(8):e0202391. doi: 10.1371/journal.pone.0202391., eCollection 2018. PMID:30138417<ref>PMID:30138417</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gc1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Biterova, E]]
[[Category: Hinttala, R]]
[[Category: Ruddock, L W]]
[[Category: Uusimaa, J]]
[[Category: Nhl repeat containing]]
[[Category: Protein binding]]
[[Category: Structural domain]]
[[Category: Thioredoxin-like]]
[[Category: Unknown function]]