Quarterly Reviews of Biophysics

Review Article

Protein–protein interaction and quaternary structure

Joël Janina1 c1, Ranjit P. Bahadura2 and Pinak Chakrabartia3

a1 Yeast Structural Genomics, IBBMC UMR 8619 CNRS, Université Paris-Sud, Orsay, France

a2 School of Engineering and Science, Jacobs University Bremen, Bremen, Germany

a3 Department of Biochemistry, Bose Institute, Calcutta, India


Protein–protein recognition plays an essential role in structure and function. Specific non-covalent interactions stabilize the structure of macromolecular assemblies, exemplified in this review by oligomeric proteins and the capsids of icosahedral viruses. They also allow proteins to form complexes that have a very wide range of stability and lifetimes and are involved in all cellular processes. We present some of the structure-based computational methods that have been developed to characterize the quaternary structure of oligomeric proteins and other molecular assemblies and analyze the properties of the interfaces between the subunits. We compare the size, the chemical and amino acid compositions and the atomic packing of the subunit interfaces of protein–protein complexes, oligomeric proteins, viral capsids and protein–nucleic acid complexes. These biologically significant interfaces are generally close-packed, whereas the non-specific interfaces between molecules in protein crystals are loosely packed, an observation that gives a structural basis to specific recognition. A distinction is made within each interface between a core that contains buried atoms and a solvent accessible rim. The core and the rim differ in their amino acid composition and their conservation in evolution, and the distinction helps correlating the structural data with the results of site-directed mutagenesis and in vitro studies of self-assembly.


c1 Author for correspondence: J. Janin, Yeast Structural Genomics, IBBMC UMR 8619 Université Paris-Sud, 91405 Orsay, France. Tel.: +33 1 69 15 79 66; Fax: +33 1 69 85 37 15; Email: joel.janin@u-psud.fr