title: Conformational switch of a flexible loop in human laminin receptor determines laminin-1 interaction.
abstract: The 37/67-kDa human laminin receptor(LamR) is a cell surface protein that interacts with molecules located in the extra-cellular matrix. In particular, interactions between LamR and laminins play a major role in mediating changes in the cellular environment that affect cell adhesion, neurite outgrowth, tumor growth and metastasis. The exact interaction mode of laminin-1 and LamR is not fully understood. Laminin-1 is thought to bind to LamR through interaction with the so-called peptide G (residues 161–180) and the C-terminal helix (residues 205–229). Here we performed 100-ns atomistic force field based molecular dynamics simulations to explore the structure and dynamics of LamR related to laminin-1 interactions. Our main finding is that loop 188–197 in the C-terminal region is highly flexible. It undergoes a major change resulting in a conformational switch that partially solvent exposes the R180 residue in the final part of the G peptide. So, R180 could contribute to laminin-1 binding. Projection of the simulations along the first two principal components also confirms the importance of this conformational switch in the LamR. This may be a basic prerequisite to clarify the key structural determinants of the interaction of LamR with laminin-1.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry,‘‘Drug Discovery Laboratory’’, University of Naples ‘‘FedericoII’’, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Giovanni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grottesi
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017474:Receptors, Laminin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D007797:Laminin; D017474:Receptors, Laminin; C121346:laminin 1