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
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.