View source for 27iv


==Crystal structure of the mature form of human ASPRV1 bound to self-cleavage peptide==
<StructureSection load='27iv' size='340' side='right'caption='[[27iv]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[27iv]] is a 2 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=27IV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=27IV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#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></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=27iv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=27iv OCA], [https://pdbe.org/27iv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=27iv RCSB], [https://www.ebi.ac.uk/pdbsum/27iv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=27iv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/APRV1_HUMAN APRV1_HUMAN] Lamellar ichthyosis. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/APRV1_HUMAN APRV1_HUMAN] Protease responsible for filaggrin processing, essential for the maintenance of a proper epidermis organization.<ref>PMID:32516568</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The establishment of the epidermal barrier is essential for terrestrial vertebrate survival. Retroviral-like aspartic protease 1 (ASPRV1), also known as skin aspartic protease (SASPase), plays a central role in this process by facilitating the initial cleavage of profilaggrin into filaggrin monomers, which is vital for skin hydration and barrier integrity. Mutations disrupting this activity are linked to hereditary skin disorders. Evolutionarily, ASPRV1 originated from the domestication of an ancient retroviral sequence and comprises a Gag-like domain and a C-terminal protease domain. While it shares structural similarity with HIV-1 protease (HIV-1 PR), the molecular basis for its unique enzymatic properties and substrate specificity remains unclear. Here, we present the biochemical characterization and crystal structures of mature human ASPRV1 (ASPRV1-14) in multiple states, including wild-type, catalytically inactive mutants bound to self-cleavage and filaggrin peptides, and a complex with the HIV-1 PR inhibitor indinavir. Our results demonstrate that ASPRV1-14 exhibits an ionic strength-dependent monomer-dimer equilibrium, shifting from a low-activity monomer at low ionic strength to a high-activity dimer at high ionic strength. Structural analysis reveals that ASPRV1-14 possesses distinctly hydrophobic S2/S2' pockets, dictating a strict requirement for hydrophobic residues at the P2/P2' positions of substrates and explaining its resistance to most HIV-1 PR inhibitors, except indinavir. Furthermore, analysis of disease-associated mutations indicates two main pathogenic mechanisms: disrupting the S2/S2' pocket ( e. g., V243A) or interfering with the self-cleavage maturation process ( e. g., I186T, K199E, R311C/P, and P314T). Collectively, these findings provide a comprehensive molecular framework for understanding the roles of ASPRV1 in epidermal homeostasis and the pathogenesis of skin diseases, offering insights for future therapeutic development.

Structure and enzymatic properties of human retroviral-like aspartic protease 1 and functional roles of disease-associated mutations.,Feng X, Chen Z, Lan C, Ding J Acta Biochim Biophys Sin (Shanghai). 2026 Aug 11. doi: 10.3724/abbs.2026141. PMID:42593882<ref>PMID:42593882</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 27iv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen Z]]
[[Category: Ding J]]
[[Category: Feng X]]