9I5A

Crystal structure of wild type perlecan region 3 construct I876-V1272 construct including one laminin IV-like and four laminin EGF-like domains.

Summary for 9I5A

• Entry DOI: 10.2210/pdb9i5a/pdb
• Descriptor: Basement membrane-specific heparan sulfate proteoglycan core protein, SUCCINIC ACID, GLYCEROL, ... (4 entities in total)
• Functional Keywords: basement membrane proteins; perlecan;laminin iv-like; laminin egf-like domains, structural protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 86194.65

Authors

Sohail, A.A.,Koski, M.K.,Ruddock, L.R. (deposition date: 2025-01-27, release date: 2025-04-02, Last modification date: 2025-05-21)

Primary citation

Sohail, A.A.,Koski, M.K.,Ruddock, L.W.
Structural insights on perlecan and Schwartz-Jampel syndrome.
Matrix Biol., 138:1-7, 2025

PubMed Abstract: Perlecan 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.

PubMed: 40118124
DOI: 10.1016/j.matbio.2025.03.002

Experimental method

X-RAY DIFFRACTION (2.045 Å)