A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules

Tong, Amy; Drees, Becky; Nardelli, Giuliano; Bader, Gary D.; Brannetti, Barbara; Castagnoli, Luisa; Evangelista, Marie; Ferracuti, Silvia; Nelson, Bryce; Paoluzi, Serena; Quondam, Michele; Zucconi, Adriana; Hogue, Christopher W. V.; Fields, Stanley; Boone, Charles; Cesareni, Gianni

doi:10.1126/science.1064987

Cited by 652 publications

(493 citation statements)

References 20 publications

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“…Largescale proteomic studies have also demonstrated interactions between Las17 and Ysc84, including isolation in complexes from cells (Gavin et al, 2002;Tong et al, 2002;Landgraf et al, 2004;Tarassov et al, 2008). However, to date, no role has been shown for Ysc84 in endocytosis.…”

Section: Function Of Ysc84 In Endocytosismentioning

confidence: 99%

The WASP Homologue Las17 Activates the Novel Actin-regulatory Activity of Ysc84 to Promote Endocytosis in Yeast

Robertson¹,

Allwood²,

Smith³

et al. 2009

MBoC

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Actin plays an essential role in many eukaryotic cellular processes, including motility, generation of polarity, and membrane trafficking. Actin function in these roles is regulated by association with proteins that affect its polymerization state, dynamics, and organization. Numerous proteins have been shown to localize with cortical patches of yeast actin during endocytosis, but the role of many of these proteins remains poorly understood. Here, we reveal that the yeast protein Ysc84 represents a new class of actin-binding proteins, conserved from yeast to humans. It contains a novel N-terminal actin-binding domain termed Ysc84 actin binding (YAB), which can bind and bundle actin filaments. Intriguingly, full-length Ysc84 alone does not bind to actin, but binding can be activated by a specific motif within the polyproline region of the yeast WASP homologue Las17. We also identify a new monomeric actin-binding site on Las17. Together, the polyproline region of Las17 and Ysc84 can promote actin polymerization. Using live cell imaging, kinetics of assembly and disassembly of proteins at the endocytic site were analyzed and reveal that loss of Ysc84 and its homologue Lsb3 decrease inward movement of vesicles consistent with a role in actin polymerization during endocytosis.

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Section: Function Of Ysc84 In Endocytosismentioning

confidence: 99%

The WASP Homologue Las17 Activates the Novel Actin-regulatory Activity of Ysc84 to Promote Endocytosis in Yeast

Robertson¹,

Allwood²,

Smith³

et al. 2009

MBoC

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“…A consensus sequence PxxxPPxxP has been reported as the ligand for the type I myosin SH3 domains, and a single predicted ligand is present within the last 12 residues of the PRD of Pan1 (Tong et al, 2002). To test whether this Cterminal ligand is important for the interaction between Pan1 and the myosins, we made a truncated construct, His 6 -Pan1 PRD⌬12 (aa1310 -1468), in which the last 12 amino acids were removed.…”

Section: The Pan1 Prd Directly Interacts With the Sh3 Domains Of The mentioning

confidence: 99%

Interaction of the Endocytic Scaffold Protein Pan1 with the Type I Myosins Contributes to the Late Stages of Endocytosis

Barker

Lee

Pierce

et al. 2007

MBoC

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“…Confidence yeast two-hybrid [32][33][34][35] or affinity purification of complexes 36,37 ) data sets and obtain a tolerably accurate view of the total possible network of interactions that might occur between cellular proteins. Links seen in multiple data sets (even if each of these is very noisy) reinforce and greatly improve the quality of the network; thus, even links observed in weak or noisy data sets are of value as they may sum with other such links to form statistically significant informational interactions.…”

Section: Low High Mediummentioning

confidence: 99%

A probabilistic view of gene function

2004

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Cells are controlled by the complex and dynamic actions of thousands of genes. With the sequencing of many genomes, the key problem has shifted from identifying genes to knowing what the genes do; we need a framework for expressing that knowledge. Even the most rigorous attempts to construct ontological frameworks describing gene function (e.g., the Gene Ontology project) ultimately rely on manual curation and are thus labor-intensive and subjective. But an alternative exists: the field of functional genomics is piecing together networks of gene interactions, and although these data are currently incomplete and error-prone, they provide a glimpse of a new, probabilistic view of gene function. We outline such a framework, which revolves around a statistical description of gene interactions derived from large, systematically compiled data sets. In this probabilistic view, pleiotropy is implicit, all data have errors and the definition of gene function is an iterative process that ultimately converges on the correct functions. The relationships between the genes are defined by the data, not by hand. Even this comprehensive view fails to capture key aspects of gene function, not least their dynamics in time and space, showing that there are limitations to the model that must ultimately be addressed.The necessity for a logical framework A primary issue in biology is describing the global organization of genes into systems and understanding the coordination of these systems in the cell. The sequencing of complete genomes has yielded the full parts lists of several organisms, and we now have powerful techniques to sample different aspects of gene function at a genome-wide level. Together, these advances hold great promise in leading us closer to a complete description of the molecular biology of the cell. For us to reach this goal, however, we need some coherent framework in which to express what we learn about gene function through the accumulation of data. What do we mean by 'gene function'? More importantly, what should we mean by this? What are the key properties of genes that we should measure to adequately describe their function in the cell? If we have all the measurements, how should we integrate them into a complete description of the molecular machineries that are the basis of a cell? Our framework for thinking about gene function inevitably colors the questions we ask and the conclusions we draw; therefore, defining a rational framework is not merely an exercise in abstraction but a key tool in understanding how an organism works.Great effort (e.g., refs. 1-8) has already gone into defining precisely what we mean by the functions of genes, as well as how we should record this information. These summaries help us by identifying common features of genes with similar functions and giving clues to the organization and control of processes in the cell. They may also help us to see whether this organization can explain observed biological properties and guide us toward new processes. The functional framework itsel...

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A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules

Cited by 652 publications

References 20 publications

The WASP Homologue Las17 Activates the Novel Actin-regulatory Activity of Ysc84 to Promote Endocytosis in Yeast

The WASP Homologue Las17 Activates the Novel Actin-regulatory Activity of Ysc84 to Promote Endocytosis in Yeast

Interaction of the Endocytic Scaffold Protein Pan1 with the Type I Myosins Contributes to the Late Stages of Endocytosis

A probabilistic view of gene function

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