title: Effects of altered restraints in beta1 integrin on the force-regulated interaction between the glycosylated I-like domain of beta1 integrin and fibronectin III9-10: a steered molecular dynamic study.
abstract: Cytoskeletal restraints affect force-regulated integrin function in cell adhesion. However, the structural and molecular basis underlying the effect of cytoskeletal restraints on beta1 integrin binding to fibronectin is still largely unknown. In this study, we used steered molecular dynamics simulations to investigate the changes in glycosylated beta1 integrin-fibronectin binding and in conformation and structure of the glycosylated beta1 I-like domain-FN-III9-10 complex caused by altered restraints applied to beta1 I-like domain. The results revealed that imposition of the increased constraints on beta1 integrin increased resistance to force-induced dissociation of the beta1 I-like domain-fibronectin complex. Specifically, the increased constraints enhanced resistance to relative conformational changes in the RGD-synergy site in fibronectin, increased the conformational stability of fibronectin, and prevented losses in hydrogen bond occupancy of each beta-strand pair in FN-III10 resulting from external force. The increased constraints also resulted in an increase in correlated motion between residues in the beta1 I-like domain, which may directly affect the interaction of beta1 integrin with fibronectin. Results from this study provide molecular and structural insights into the effects of altered restraints in beta1 integrin on the interaction between glycosylated beta1 Integrin and fibronectin and its induced cell adhesion.
authors: Department of Biomedical Engineering, The University of Alabama at Birmingham, 803 Shelby Interdisciplinary Biomedical Research Building, 1825 University Boulevard, Birmingham, AL 35294, USA.
authors: Di
authors: D
authors: Pan
authors: Yuhua
authors: Y
authors: Song
mesh_terms: D001665:Binding Sites; D002448:Cell Adhesion; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D006860:Hydrogen Bonding; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000093844:Glycated Proteins
chemical_list: D005353:Fibronectins; D017127:Glycation End Products, Advanced; D019012:Integrin beta1; C045099:glycated fibronectin; D000093844:Glycated Proteins