ABSTRACT

Malgorzata E. Kokoszka, Zhaozhong Han, Ece Karatan, and Brian K. Kay

9.1 INTRODUCTION

In recent years, it has become well recognized that eukaryotic cells utilize protein-protein interactions for a number of cellular processes, such as assembly of the cytoskeleton, transference of signals during signal transduction, and to compartmentalize proteins. Across different eukaryotic organisms, the predicted number of protein-protein interactions ranges from tens to hundreds of thousands [1]. Protein interaction modules often serve to mediate such protein-protein interactions [2] and have the following properties: they are typically 60-140 amino acids in length, fold autonomously within the context of the protein that contains the modular domain, and bind segments of other proteins known as short linear motifs (SLiMs), ranging

CONTENTS

9.1 Introduction .................................................................................................. 229 9.2 Domain-Mediated Interactions ..................................................................... 231

9.2.1 EH Domains .................................................................................... 231 9.2.2 SH3 Domains ................................................................................... 231 9.2.3 PDZ Domains ..................................................................................234 9.2.4 WW Domains .................................................................................. 236 9.2.5 PTB and SH2 Domains ................................................................... 237 9.2.6 Chromo Shadow Domain ................................................................ 239

9.3 Nondomain-Mediated Protein-Protein Interactions ....................................240 9.4 Software for Identifying Candidate Interacting Partners .............................240 9.5 Analyzing Predicted Interactions ................................................................. 241 9.6 Relevance to Biotechnology and Drug Discovery ........................................242 References .............................................................................................................. 243

from 2 to 11 amino acids in length [3,4]. Examples include the Eps15 homology (EH) domain, the phosphotyrosine-binding (PTB) domain, the postsynaptic density/disclarge/ZO1 (PDZ) domain, the Src homology (SH) 2 and 3 domains, and the WW domain (Figure 9.1).