Comparative analysis of Saccharomyces cerevisiae WW domains and their interacting proteins.
BACKGROUND
The WW domain is found in a large number of eukaryotic proteins implicated in a variety of cellular processes. WW domains bind proline-rich protein and peptide ligands, but the protein interaction partners of many WW domain-containing proteins in Saccharomyces cerevisiae are largely unknown.


RESULTS
We used protein microarray technology to generate a protein interaction map for 12 of the 13 WW domains present in proteins of the yeast S. cerevisiae. We observed 587 interactions between these 12 domains and 207 proteins, most of which have not previously been described. We analyzed the representation of functional annotations within the network, identifying enrichments for proteins with peroxisomal localization, as well as for proteins involved in protein turnover and cofactor biosynthesis. We compared orthologs of the interacting proteins to identify conserved motifs known to mediate WW domain interactions, and found substantial evidence for the structural conservation of such binding motifs throughout the yeast lineages. The comparative approach also revealed that several of the WW domain-containing proteins themselves have evolutionarily conserved WW domain binding sites, suggesting a functional role for inter- or intramolecular association between proteins that harbor WW domains. On the basis of these results, we propose a model for the tuning of interactions between WW domains and their protein interaction partners.


CONCLUSIONS
Protein microarrays provide an appealing alternative to existing techniques for the construction of protein interaction networks. Here we built a network composed of WW domain-protein interactions that illuminates novel features of WW domain-containing proteins and their protein interaction partners.
Hesselberth
Jay R
JR
Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, USA.
Miller
John P
JP
Golob
Anna
A
Stajich
Jason E
JE
Michaud
Gregory A
GA
Fields
Stanley
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D005075:Biological Evolution; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D040081:Protein Array Analysis / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D016415:Sequence Alignment; D015003:Yeasts / Q000145:classification / Q000235:genetics
D008024:Ligands; D029701:Saccharomyces cerevisiae Proteins