Artificial intelligence and the analysis of cryo-EM data provide structural insight into the molecular mechanisms underlying LN-lamininopathies.

ABSTRACT: Laminins (Lm) are major components of basement membranes (BM), which polymerize to form a planar lattice on cell surface. Genetic alternations of Lm affect their oligomerization patterns and lead to failures in BM assembly manifesting in a group of human disorders collectively defined as Lm N-terminal domain lamininopathies (LN-lamininopathies). We have employed a recently determined cryo-EM structure of the Lm polymer node, the basic repeating unit of the Lm lattice, along with structure prediction and modeling to systematically analyze structures of twenty-three pathogenic Lm polymer nodes implicated in human disease. Our analysis provides the detailed mechanistic explanation how Lm mutations lead to failures in Lm polymerization underlining LN-lamininopathies. We propose the new categor

SUBMITTER: Kulczyk AW 

PROVIDER: S-EPMC10587063 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature