A CD2-based model of yeast alpha-agglutinin elucidates solution properties and binding characteristics.
We have previously shown that the Saccharomyces cerevisiae cell adhesion protein alpha-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 alpha-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 alpha-agglutinin domains constructed on the basis of these alignments were shown to conform to peptide mapping data and biophysical properties of alpha-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 alpha -agglutinin and the hydrophobic nature of binding to its peptide ligand alpha-agglutinin. The procedures used to align the alpha-agglutinin sequence and test the quality of the model may be applicable to other proteins, especially those that resist crystallization because of extensive glycosylation.
Grigorescu
A
A
Department of Biological Sciences and The Institute for Biomolecular Structure and Function, Hunter College of the City University of New York, NY 10021, USA.
Chen
M H
MH
Zhao
H
H
Kahn
P C
PC
Lipke
P N
PN
D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D018801:CD2 Antigens / Q000737:chemistry* / Q000378:metabolism*; D015704:CD4 Antigens / Q000737:chemistry; D002448:Cell Adhesion; D004220:Disulfides; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008024:Ligands; D000072235:Mating Factor; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012984:Software
D000596:Amino Acids; D018801:CD2 Antigens; D015704:CD4 Antigens; D004220:Disulfides; D007136:Immunoglobulins; D008024:Ligands; D010455:Peptides; D000072235:Mating Factor