circularly permuted PDZ domain of high-temperature requirement factor A (HtrA) family serine proteases and related domains
PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of HtrA family serine proteases including human HtrA1, HtrA2 (mitochondrial), HtrA3, and HtrA4, and related domains. These proteases are key enzymes associated with pregnancy. Their diverse biological functions include cell growth proliferation, migration and apoptosis. They are also implicated in disorders including Alzheimer's, Parkinson's, arthritis and cancer. HtrA1 (also known as high-temperature requirement A serine peptidase 1, L56, and serine protease 11) substrates include extracellular matrix proteins, proteoglycans, and insulin-like growth factor (IGF)-binding proteins. HtrA1 also inhibits signaling by members of the transforming growth factor beta (TGF-beta) family. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.
Feature 1:peptide binding site [polypeptide binding site]
Evidence:
Comment:based on HtrA family circularly permuted PDZ domains with structure
Comment:this is a circularly permuted variant of the canonical PDZ domain, where beta-strand A is placed after beta-strand F
Comment:PDZ domains specifically recognize and bind to short C-terminal peptide motifs, but can also recognize internal peptide motifs and certain lipids
Structure:2JOA: circularly permuted PDZ domain of human HtrA1 binds optimal phage-derived peptide H1-C1 (DSRIWWV); contacts at 4A - View structure with Cn3D
Structure:2PZD: circularly permuted PDZ domain of human HtrA2-PDZext binds the C terminal extension of HtrA2-PDZext (WTMFWV); contacts at 4A - View structure with Cn3D
Comment:HtrA2-PDZext: HtrA2 PDZ domain having an added 9-residue extension (GGGWTMFWV); WTMFWV is a phage-derived peptide
Jiyao W et al.(2023). "The conserved domain database in 2023.",