Cryo-EM, AI and MD simulations reveal the molecular basis of laminin polymer turnover and its defects associated with human disease.
Basement membranes are elastic biopolymers that form a sheet-like lattice on cell surfaces. They function not only as structural scaffolds supporting cell anchorage and tissue organization, but also as mechanosignaling platforms orchestrating cell behavior. Structural alternations of basement membranes have been implicated in a wide spectrum of human genetic disorders and tumor metastasis.
Recently, we employed cryo-EM to determine the structures of two protein-protein complexes critical for the turnover of the laminin lattice, an integral part of the basement membrane. We also applied and validated Alphafold2 to model fifty-five structures of pathogenic laminin complexes and employed the Anton2 supercomputer to probe their dynamics. Collectively, our biophysical data reveal the molecular basis of laminin lattice assembly and disassembly and provide insights into polymerization defects associated with human disease.
- References:
Kulczyk, A.W. et al. Cryo-EM reveals the molecular basis of laminin polymerization and LN-lamininopathies. Nat. Commun 14, 317-24 (2023).
Kulczyk, A.W. Artificial intelligence and the analysis of cryo-EM data provide structural insight into the molecular mechanisms underlying LN-lamininopathies. Sci. Rep. 13, 17825 (2023).
Yurchenco, P.D. & Kulczyk, A.W. Polymerizing laminins in development, health and disease. J. Biol. Chem. 300, 107429 (2024).
Hosted by Professor Lu Wang