Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins.
SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes.
Tonikian
Raffi
R
Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.
Xin
Xiaofeng
X
Toret
Christopher P
CP
Gfeller
David
D
Landgraf
Christiane
C
Panni
Simona
S
Paoluzi
Serena
S
Castagnoli
Luisa
L
Currell
Bridget
B
Seshagiri
Somasekar
S
Yu
Haiyuan
H
Winsor
Barbara
B
Vidal
Marc
M
Gerstein
Mark B
MB
Bader
Gary D
GD
Volkmer
Rudolf
R
Cesareni
Gianni
G
Drubin
David G
DG
Kim
Philip M
PM
Sidhu
Sachdev S
SS
Boone
Charles
C
D000465:Algorithms; D001499:Bayes Theorem; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis; D015966:Gene Expression Regulation, Fungal; D008024:Ligands; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019151:Peptide Library; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D018909:src Homology Domains
D002352:Carrier Proteins; D008024:Ligands; C547075:Lsb3 protein, S cerevisiae; D008840:Microfilament Proteins; D019151:Peptide Library; D029701:Saccharomyces cerevisiae Proteins; C084789:YSC84 protein, S cerevisiae