A second Ig-like domain identified in dystroglycan by molecular modelling and dynamics

Manuela Bozzi, Maria Cristina De Rosa, Davide Pirolli, Bruno Giardina, Andrea Brancaccio, Francesca Sciandra

Risultato della ricerca: Contributo in rivistaArticolo in rivista

17 Citazioni (Scopus)

Abstract

Dystroglycan (DG) is a cell surface receptor which is composed of two subunits that interact noncovalently, namely alpha- and beta-DG. In skeletal muscle, DG is the central component of the dystrophin-glycoprotein complex (DGC) that anchors the actin cytoskeleton to the extracellular matrix. To date only the three-dimensional structure of the N-terminal region of alpha-DG has been solved by X-ray crystallography. To expand such a structural analysis, a theoretical molecular model of the murine alpha-DG C-terminal region was built based on folding recognition/threading techniques. Although there is no a significant (<30\%) sequence homology with the N-terminal region of alpha-DG, protein fold recognition methods found a significant resemblance to the alpha-DG N-terminal crystallographic structure. Our in silico structural prediction identified two subdomains in this region. Amino acid residues similar to 500-600 of alpha-DG were predicted to adopt an immunoglobulin-like (Ig-like) beta-sandwich fold. Such modeled domain includes the beta-DG binding epitope of alpha-DG and, confirming our previous experimental results, suggests that the linear epitope (residues 550-565) assumes a beta-strand conformation. The remaining segment of the alpha-DG C-terminal region (residues 601-653) is organized in a coil-helix-coil motif. A 20-ns molecular dynamics simulation in explicit water solvent provided support to the predicted Ig-like model structure. The identification of a second Ig-like domain in DG represents another important step towards a full structural and functional description of the alpha/beta DG interface. Preliminary characterization of a novel recombinant peptide (505-600) encompassing this second lg-like domain demonstrates that it is soluble and stable, further corroborating our in silico analysis
Lingua originaleEnglish
pagine (da-a)1015-1024
Numero di pagine10
RivistaJOURNAL OF MOLECULAR GRAPHICS &amp; MODELLING
Volume29
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Dystroglycan
  • Ig-like fold
  • Molecular dynamics
  • Protein modelling

Fingerprint Entra nei temi di ricerca di 'A second Ig-like domain identified in dystroglycan by molecular modelling and dynamics'. Insieme formano una fingerprint unica.

Cita questo