View source for 6xov


==CryoEM structure of human presequence protease in partial closed state 1==
<StructureSection load='6xov' size='340' side='right'caption='[[6xov]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xov]] is a 3 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=6XOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XOV 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]] 3.3&#8491;</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=6xov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xov OCA], [https://pdbe.org/6xov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xov RCSB], [https://www.ebi.ac.uk/pdbsum/6xov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xov ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PREP_HUMAN PREP_HUMAN] ATP-independent protease that degrades mitochondrial transit peptides after their cleavage. Also degrades other unstructured peptides. Specific for peptides in the range of 10 to 65 residues. Able to degrade amyloid beta A4 (APP) protein when it accumulates in mitochondrion, suggesting a link with Alzheimer disease. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference.<ref>PMID:16849325</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Presequence protease (PreP), a 117 kDa mitochondrial M16C metalloprotease vital for mitochondrial proteostasis, degrades presequence peptides cleaved off from nuclear-encoded proteins and other aggregation-prone peptides, such as amyloid beta (Abeta). PreP structures have only been determined in a closed conformation; thus, the mechanisms of substrate binding and selectivity remain elusive. Here, we leverage advanced vitrification techniques to overcome the preferential denaturation of one of two ~55 kDa homologous domains of PreP caused by air-water interface adsorption. Thereby, we elucidate cryoEM structures of three apo-PreP open states along with Abeta- and citrate synthase presequence-bound PreP at 3.3-4.6 A resolution. Together with integrative biophysical and pharmacological approaches, these structures reveal the key stages of the PreP catalytic cycle and how the binding of substrates or PreP inhibitor drives a rigid body motion of the protein for substrate binding and catalysis. Together, our studies provide key mechanistic insights into M16C metalloproteases for future therapeutic innovations.

Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition.,Liang WG, Wijaya J, Wei H, Noble AJ, Mancl JM, Mo S, Lee D, Lin King JV, Pan M, Liu C, Koehler CM, Zhao M, Potter CS, Carragher B, Li S, Tang WJ Nat Commun. 2022 Apr 5;13(1):1833. doi: 10.1038/s41467-022-29322-4. PMID:35383169<ref>PMID:35383169</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xov" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Liang WG]]
[[Category: Tang W]]
[[Category: Zhao M]]