PROTEIN-PROTEIN INTERFACES - ARCHITECTURES AND INTERACTIONS IN PROTEIN-PROTEIN INTERFACES AND IN PROTEIN CORES - THEIR SIMILARITIES AND DIFFERENCES

Protein structures generally consist of favorable folding motifs forme d by specific arrangements of secondary structure elements. Similar ar chitectures can be adopted by different amino acids sequences, althoug h the details of the structures vary. It has long been known that desp ite the sequence variability, there is a striking preferential conserv ation of the hydrophobic character of the amino acids at the buried po sitions of these folding motifs. Differences in the sizes of the side- chains are accommodated by movements of the secondary structure elemen ts with respect to each other, leading to compact packing. Scanning pr otein-protein interfaces reveals that similar architectures are also o bserved at and around their interacting surfaces, with preservation of the hydrophobic character, although not to the same extent. The gener al forces that determine the origin of the native structures of protei ns have been investigated intensively. The major non-bonded forces ope rating on a protein chain as it folds into a three-dimensional structu re are likely to be packing, the hydrophobic effect, and electrostatic interactions. While the substantial hydrophobic forces lead to a comp act conformation, they are also nonspecific and cannot serve as a guid e to a conformationally unique structure. For the general folding prob lem, it thus appears that packing is a prime candidate for determining a particular fold. Specific hydrogen-bonding patterns and salt-bridge s have also been proposed to play a role. Inspection of protein-protei n interfaces reveals that the hallmarks governing single chain protein structures also determine their interactions, suggesting that similar principles underlie protein folding and protein-protein associations. This review focuses on some aspects of protein-protein interfaces, pa rticularly on the architectures and their interactions. These are comp ared with those present in protein monomers. This task is facilitated by the recently compiled, non-redundant structural dataset of protein- protein interfaces derived from the crystallographic database. In part icular, although current view holds that protein-protein interfaces an d interactions are similar to those found in the conformations of sing le-chain proteins, this review brings forth the differences as well. N ot only is it logical that such differences would exist, it is these d ifferences that further illuminate protein folding on the one hand and protein-protein recognition on the other. These are also particularly important in considering inhibitor (ligand) design.