Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins

Tonikian, Raffi; X, Xin; Toret, Christopher P.; Gfeller, David; Landgraf, Christiane; Panni, Simona; Paoluzi, Serena; Castagnoli, Luisa; Currell, Bridget; Seshagiri, Somasekar; Yu, Haiyuan; Winsor, Barbara; Vidal, Marc; Gerstein, Mark; Bader, Gary D.; Volkmer, Rudolf; Cesareni, Gianni; Drubin, David G.; Kim, Philip M.; Sidhu, Sachdev S.; Boone, Charles

doi:10.1371/journal.pbio.1000218

Cited by 177 publications

(303 citation statements)

References 57 publications

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“…The binding affinity was obtained from the work of Tonikian et al (27), in which SH3 binding peptides were identified by SPOT peptide arrays, and then their binding specificity was scored based on signal intensity. In total, 295 peptides showed positive signal with at least one SH3 domain.…”

Section: Methodsmentioning

confidence: 99%

“…A number of in vitro methods have been applied to study preferences of SH3 domains for specific sequence patterns, i.e., motifs. These methods include protein microarrays (26), synthetic peptide arrays (27), and screening of phage-displayed peptide libraries against Significance Today, we understand how short linear peptides bind to distinct recognition domains. However, at the cellular level, we still do not grasp why certain binding peptides are highly specific, whereas others are highly cross-reactive, and also what is the relationship with the functions of domain-peptide interactions.…”

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confidence: 99%

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Evolution of domain–peptide interactions to coadapt specificity and affinity to functional diversity

Kelil

Levy

Michnick

2016

Proc. Natl. Acad. Sci. U.S.A.

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Evolution of complexity in eukaryotic proteomes has arisen, in part, through emergence of modular independently folded domains mediating protein interactions via binding to short linear peptides in proteins. Over 30 years, structural properties and sequence preferences of these peptides have been extensively characterized. Less successful, however, were efforts to establish relationships between physicochemical properties and functions of domainpeptide interactions. To our knowledge, we have devised the first strategy to exhaustively explore the binding specificity of protein domain-peptide interactions. We applied the strategy to SH3 domains to determine the properties of their binding peptides starting from various experimental data. The strategy identified the majority (∼70%) of experimentally determined SH3 binding sites. We discovered mutual relationships among binding specificity, binding affinity, and structural properties and evolution of linear peptides. Remarkably, we found that these properties are also related to functional diversity, defined by depth of proteins within hierarchies of gene ontologies. Our results revealed that linear peptides evolved to coadapt specificity and affinity to functional diversity of domain-peptide interactions. Thus, domain-peptide interactions follow human-constructed gene ontologies, which suggest that our understanding of biological process hierarchies reflect the way chemical and thermodynamic properties of linear peptides and their interaction networks, in general, have evolved.linear peptides | domain-peptide interactions | binding specificity | binding affinity | functional specificity M any proteins, particularly in eukaryotes, are composed of modular protein architectures consisting of multiple independently folding domains (1). Specific domains such as SH3 and PDZ domains were repeatedly used throughout evolution in increasingly complex organisms to mediate protein-protein interactions involved in signal transduction and protein targeting (2-5). These domains are associated with a number of human diseases and are targets of virus and other pathogen virulence proteins (6). Functions of these domains include binding to sequence-specific peptides both among themselves and on other proteins. Such interactions can create enormous plasticity in complex signaling and regulatory networks on immediate to evolutionary timescales (7), and are often used for regulating the activities of proteins and the spatiotemporal organization of protein interaction networks (8,9). However, at the cellular level, we still do not grasp why certain peptides in proteins bind to distinct domains with high specificity whereas others highly cross-react with a number of members of a family of domains, and also what is the relationship between specificity of binding and specificity of functions of domain-peptide interactions. Two extreme examples are peptides of the MAPKK protein Pbs2 (residues 92-106) (10) and the actin assembly protein Las17 (residues 306-336) (11), which both interact with ...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Evolution of domain–peptide interactions to coadapt specificity and affinity to functional diversity

Kelil

Levy

Michnick

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The arrays were designed using in-house LISA software. Cellulose-(3-amino-2-hydroxypropyl)-ether membranes gave a better signal/noise ratio compared with standard ␤-alanine cellulose membranes (26,27).…”

Section: Synthesis Of Soluble Peptides and Microarraysmentioning

confidence: 99%

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)

Rouka

Simister

Janning

et al. 2015

Journal of Biological Chemistry

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Background:The CD2AP adaptor facilitates cell signaling using its in-built interaction modules (SH3 domains). Results: RIN3 was characterized as a novel CD2AP SH3 binding protein by biophysical and biochemical methods. Conclusion: CD2AP has many potential interactors and is probably a cellular hub. Significance: We reveal how protein modules can interact with families of related recognition motifs rather than a single motif.

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“…Subsequently, the same sequencing was used by several groups to monitor selection of binding proteins from a library of open reading frames (ORF) displayed on phage [6,7]. Sidhu and co-workers used 454-sequencing to boost selection of peptides binding to different PDZ domains [8][9][10]. Notably, the authors used barcoded primers for the preparation of library for sequencing and, thus, sequenced 22 independent panning experiments in one run.…”

Section: Introductionmentioning

confidence: 99%

Deep sequencing analysis of phage libraries using Illumina platform

Matochko

Chu

Jin

et al. 2012

Methods

105

110

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This paper presents an analysis of phage-displayed libraries of peptides using Illumina. We describe steps for the preparation of the short DNA fragments for deep sequencing and MatLab software for the analysis of the results. Screening of peptide libraries displayed on the surface of bacteriophage (phage display) can be used to discover peptides that bind to any target. The key step in this discovery is the analysis of peptide sequences present in the library. This analysis is usually performed by Sanger sequencing, which is labor intensive and limited to examination of a few hundred phage clones. On the other hand, Illumina deep-sequencing technology can characterize over 10 7 reads in a single run. We applied Illumina sequencing to analyze phage libraries. Using PCR, we isolated variable regions from a M13KE phage vector. The PCR primers contained (i) sequences flanking the variable region, (ii) barcodes, and (iii) variable 5'-terminal region. We used this approach to examine how diversity of peptides in phage display libraries changes as a result of amplification of libraries in bacteria. Using HiSeq single-end Illumina sequencing of these fragments, we acquired over 2x10 7 reads, 57 base pairs (bp) in length. Each read contained information about the barcode (6 bp), one complimentary region (12 bp) and a variable region (36 bp). We applied this sequencing to a model library of 10 6 unique clones and observed that amplification enriches ~150 clones, which dominate ~20% of the library. Deep sequencing, for the first time, characterized the collapse of diversity in phage libraries. The results suggest that screens based on repeated amplification and small-scale sequencing identify a few binding clones and miss thousands of useful clones. The deep sequencing approach described here could identify under-represented clones in phage screens. It could also be instrumental in developing new screening strategies, which can preserve diversity of phage clones and identify ligands previously lost in phage display screens.

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Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins

Abstract: A genome-scale specificity and interaction map for yeast SH3 domain-containing proteins reveal how family members show selective binding to target proteins and predicts the dynamic localization of new candidate endocytosis proteins.

Cited by 177 publications

References 57 publications

Evolution of domain–peptide interactions to coadapt specificity and affinity to functional diversity

Evolution of domain–peptide interactions to coadapt specificity and affinity to functional diversity

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)

Deep sequencing analysis of phage libraries using Illumina platform

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