Deciphering Protein鈥揚rotein Interactions. Part I. Experimental Techniques and Databases

摘要

It is now becoming clear that protein interactions determine the outcome of most cellular processes [1–4]. Therefore, identifying and characterizing protein–protein interactions and their networks is essential for understanding the mechanisms of biological processes on a molecular level. Despite the fact that protein interactions are remarkably diverse, all protein interfaces share certain common properties. Protein interactions can be classified into different types depending on their strength (permanent and transient), specificity (specific or nonspecific), the location of interacting partners within one or on two polypeptide chains, and the similarity between interacting subunits (homo- and hetero-oligomers). It has been shown that interface types are significantly different in amino acid composition so that it is possible to predict the type of interaction interface from amino acid composition alone [5]. Earlier structural analysis of interfaces showed that most interfaces consist of completely buried cores surrounded by partially accessible rims [6,7] with the overall size of about 1600 ± 400 ?2 (a “standard size” patch) [8]. It has been found that certain amino acids are preferred on protein interfaces and that the amino acid composition of the core differs considerably from the rim [6,7,9,10]. More recent models suggested that the protein binding site consists of a few independent highly packed regions, so called “hot spots,” which contribute significantly to the free energy of binding [11–13]. Hot spots were found to be structurally conserved [14], and the energetics of interactions at the hot spots have been analyzed in several studies [15–18].