View source for 8k17


==Human collagen prolyl processing enzyme complex, P3H1/CRTAP/PPIB heterotrimer, bound to collagen alpha-1(I) chain==
<StructureSection load='8k17' size='340' side='right'caption='[[8k17]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8k17]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8K17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8K17 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]] 3.18&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</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=8k17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8k17 OCA], [https://pdbe.org/8k17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8k17 RCSB], [https://www.ebi.ac.uk/pdbsum/8k17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8k17 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/P3H1_HUMAN P3H1_HUMAN] Osteogenesis imperfecta type 2;Osteogenesis imperfecta type 3. The disease is caused by variants affecting the gene represented in this entry. A splice site mutation leading to the absence of isoform 1 has been reported in 2 OI8 patients. Isoform 1 is the only form predicted to be located in the endoplasmic reticulum, which the appropriate location for the catalysis of collagen hydroxylation. These patients show indeed severely reduced COL1A1 hydroxylation (PubMed:19088120).<ref>PMID:19088120</ref> 
== Function ==
[https://www.uniprot.org/uniprot/P3H1_HUMAN P3H1_HUMAN] Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.<ref>PMID:10951563</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Collagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders.

The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex.,Li W, Peng J, Yao D, Rao B, Xia Y, Wang Q, Li S, Cao M, Shen Y, Ma P, Liao R, Qin A, Zhao J, Cao Y Nat Commun. 2024 Sep 8;15(1):7844. doi: 10.1038/s41467-024-52321-6. PMID:39245686<ref>PMID:39245686</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8k17" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao M]]
[[Category: Cao Y]]
[[Category: Li S]]
[[Category: Li W]]
[[Category: Liao R]]
[[Category: Ma P]]
[[Category: Peng J]]
[[Category: Qin A]]
[[Category: Rao B]]
[[Category: Shen Y]]
[[Category: Wang Q]]
[[Category: Xia Y]]
[[Category: Yao D]]
[[Category: Zhao J]]