Topic Introduction

Phage-Display Methodology for the Study of Protein-Protein Interactions: Overview

Adapted from "Phage-Display Methodology for the Study of Protein-Protein Interactions," Chapter 9, in Protein-Protein Interactions, 2nd edition (eds. Golemis and Adams). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA, 2005.

INTRODUCTION

In recent years, phage display has evolved into a powerful tool providing opportunities to define natural protein-protein interactions and to mold novel ligand receptors. The essential advantages of phage-display approaches originate in the incorporation of the protein and genetic components into a single phage particle. By providing a direct physical link between the expressed protein and the encoding genetic information, clones with desirable functional capacities can be efficiently subjected to iterative rounds of selection, followed by amplification of the selected sublibrary. Hence, during library selection (or panning), specific phage clones are progressively enriched on the basis of their specificity and affinity for ligand. Thus, relatively rare ligand-binding clones can be rescued rapidly and efficiently from large libraries. As these expression cloning systems have matured, versatile selection methods have been reported that are based on the functional properties of displayed proteins in diverse immunochemical and biological settings. This article summarizes phage-display methodology, including relevant biology, nucleotide-doping strategies, and considerations for library design.