title: Binding of integrin α1 to bone morphogenetic protein receptor IA suggests a novel role of integrin α1β1 in bone morphogenetic protein 2 signalling.
abstract: Here, we observed that integrin α1β1 and bone morphogenetic protein receptor (BMPR) IA formed a complex and co-localised in several cell types. However, the molecular interaction between these two molecules was not studied in detail to date and the role of the interaction in BMPR signalling remains unknown; thus, these were investigated here. In a steered molecular dynamics (SMD) simulation, the observed development of the rupture force related to the displacement between the A-domain of integrin α1 and the extracellular domain of BMPR IA indicated a strong molecular interaction within the integrin-BMPR complex. Analysis of the intermolecular forces revealed that hydrogen bonds, rather than salt bridges, are the major contributors to these intermolecular interactions. By using Enzyme-linked immunosorbent assay (ELISA) and co-immunoprecipitation (co-IP) experiments with site-directed mutants, we found that residues 85-89 in BMPR IA play the most important role for BMPR IA binding to integrin α1β1. These residues are the same as those responsible for bone morphogenetic protein 2 (BMP-2)/BMPR IA binding. In our experiments, we also found that the interference of integrin α1β1 up regulated the level of phosphorylated Smad1, 5, 8, which is the downstream of BMP/BMPR signalling. Therefore, our results suggest that integrin α1β1/BMPR IA may block BMP-2/BMPR IA complex information and interfere with the BMP-2 signalling pathway in cells.
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering, Tsinghua University, Beijing 100084, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zu
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering, Tsinghua University, Beijing 100084, PR China; Department of Mechanical and Aerospace Engineering, University of California, La Jolla, San Diego, CA 92093, USA.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering, Tsinghua University, Beijing 100084, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering, Tsinghua University, Beijing 100084, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering, Tsinghua University, Beijing 100084, PR China. Electronic address: yangchun@tsinghua.edu.cn.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins; D016466:CHO Cells; D003412:Cricetulus; D039423:Integrin alpha1 / Q000378:metabolism*; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010006:Osteoblasts / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D016212:Transforming Growth Factor beta; C498212:Bmpr1a protein, mouse; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Bone morphogenetic protein receptor IA; Integrin α1β1; Steered molecular dynamics simulation