Homology modeling of an immunoglobulin‐like domain in the Saccharomyces cerevisiae adhesion protein α‐agglutinin

Peter N. Lipke, Min‐Hao ‐H Chen, Hans De Nobel, Janet Kurjan, Peter C. Kahn

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The Saccharomyces cerevisiae adhesion protein α‐agglutinin is expressed by cells of α mating type. On the basis of sequence similarities, α‐agglutinin has been proposed to contain variable‐type immunoglobulin‐like (IgV) domains. The low level of sequence similarity to IgV domains of known structure made homology modeling using standard sequence‐based alignment algorithms impossible. We have therefore developed a secondary structure‐based method that allowed homology modeling of α‐agglutinin domain III, the domain most similar to IgV domains. The model was assessed and where necessary refined to accommodate information obtained by biochemical and molecular genetic approaches, including the positions of a disulfide bond, glycosylation sites, and proteolytic sites. The model successfully predicted surface exposure of glycosylation and proteolytic sites, as well as identifying residues essential for binding activity. One side of the domain was predicted to be covered by carbohydrate residues. Surface accessibility and volume packing analyses showed that the regions of the model that have greatest sequence dissimilarity from the IgV consensus sequence are poorly structured in the biophysical sense. Nonetheless, the utility of the model suggests that these alignment and testing techniques should be of general use for building and testing of models of proteins that share limited sequence similarity with known structures.

Original languageEnglish (US)
Pages (from-to)2168-2178
Number of pages11
JournalProtein Science
Volume4
Issue number10
DOIs
StatePublished - Oct 1995

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Keywords

  • cell adhesion molecule
  • glycoprotein
  • homology modeling
  • immunoglobulin variable domain
  • secondary structure prediction
  • sequence alignment
  • surface accessibility
  • volume packing

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