9i5b
From Proteopedia
Crystal structure of perlecan region 3 mutant (P1019L) construct I876-V1272 including one laminin IV-like and four laminin EGF-like domains.
Structural highlights
FunctionPGBM_MOUSE Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development (By similarity).[1] [2] Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6 (By similarity).[3] [4] The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity (By similarity).[5] [6] Publication Abstract from PubMedPerlecan is an essential multi-domain, disulfide bond rich basement membrane protein. Mutations in perlecan cause Schwartz-Jampel syndrome and dyssegmental dysplasia. While there has been a large body of experimental work reported on perlecan, there is only minimal structural information available to date. There is no prior structural data for region 3 of perlecan in which some Schwartz-Jampel syndrome causing point mutations have been reported. Here, we produce constructs of the disulfide rich region 3 of perlecan along with five mutations previously reported to cause Schwatz-Jampel syndrome. Four of the mutations resulted in decreased yields and thermal stability compared to the wild-type protein. In contrast, the P1019L mutation was produced in good yields and showed higher thermal stability than the wild-type protein. The crystal structures for both the wild-type and P1019L mutation were solved. As expected, both showed laminin IV-like and laminin-type EGF-like domains, with the P1019L mutation resulting in only a minor conformational change in a loop region and no significant changes in regular secondary or tertiary structure. Structural insights on perlecan and Schwartz-Jampel syndrome.,Sohail AA, Koski MK, Ruddock LW Matrix Biol. 2025 Mar 19:S0945-053X(25)00026-5. doi: , 10.1016/j.matbio.2025.03.002. PMID:40118124[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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