A CD2-based model of yeast alpha-agglutinin elucidates solution propertiesand binding characteristics

Citation
A. Grigorescu et al., A CD2-based model of yeast alpha-agglutinin elucidates solution propertiesand binding characteristics, IUBMB LIFE, 50(2), 2000, pp. 105-113
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
IUBMB LIFE
ISSN journal
1521-6543 → ACNP
Volume
50
Issue
2
Year of publication
2000
Pages
105 - 113
Database
ISI
SICI code
1521-6543(200008)50:2<105:ACMOYA>2.0.ZU;2-C
Abstract
We have previously shown that the Saccharomyces cerevisiae cell adhesion pr otein alpha -agglutinin has sequence characteristics of immunoglobulin-like proteins and have successfully modeled residues 200-325, based on the stru cture of immunoglobulin variable-type domains. Alignments matching residues 20-200 of alpha -agglutinin with domains I and II of members of the CD2/CD 4 subfamily of the immunoglobulin superfamily showed >80% conservation of k ey residues despite low sequence similarity overall. Three-dimensional mode ls of two alpha -agglutinin domains constructed on the basis of these align ments were shown to conform to peptide mapping data and biophysical propert ies of alpha -agglutinin, In addition, the residue volume and surface acces sibility characteristics of these models resembled those of the well-packed structures of related proteins. Residue-by-residue analysis showed that pa cking and accessibility anomalies were largely confined to glycosylated and protease-susceptible loop regions of the domains. Surface accessibility of hydrophobic residues was typical of proteins with extensive domain interac tions, a finding compatible with the hydrodynamic properties of alpha -aggl utinin and the hydrophobic nature of binding to its peptide ligand a-agglut inin, The procedures used to align the alpha -agglutinin sequence and test the quality of the model may be applicable to other proteins, especially th ose that resist crystallization because of extensive glycosylation.