Artificial intelligence and the analysis of cryo-EM data provide structural insight into the molecular mechanisms underlying LN-lamininopathies.
Sci Rep
; 13(1): 17825, 2023 10 19.
Article
em En
| MEDLINE
| ID: mdl-37857770
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 categorization scheme of LN-lamininopathies based on the insight gained from the structural analysis. Our results can help to facilitate rational drug design aiming in the treatment of Lm deficiencies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inteligência Artificial
/
Laminina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article