A CD2-based model of yeast α-agglutinin elucidates solution properties and binding characteristics

We have previously shown that the Saccharomyces cerevisiae cell adhesion protein α-agglutinin has sequence characteristics of immunoglobulin-like proteins and have successfully modeled residues 200-325, based on the structure of immunoglobulin variable-type domains. Alignments matching residues 20-200 of α-agglutinin with domains I and II of members of the CD2/CD4 subfamily of the immunoglobulin superfamily showed >80% conservation of key residues despite low sequence similarity overall. Three-dimensional models of two α-agglutinin domains constructed on the basis of these alignments were shown to conform to peptide mapping data and biophysical properties of α-agglutinin. In addition, the residue volume and surface accessibility characteristics of these models resembled those of the well-packed structures of related proteins. Residue-by-residue analysis showed that packing 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 interactions, a finding compatible with the hydrodynamic properties of α-agglutinin and the hydrophobic nature of binding to its peptide ligand a-agglutinin. The procedures used to align the α-agglutinin sequence and test the quality of the model may be applicable to other proteins, especially those that resist crystallization because of extensive glycosylation.