The third dimension for protein interactions and complexes.

Abstract Interaction discovery methods, such as the two-hybrid system and affinity purification, suggest thousands of protein–protein interactions. Structural biology provides atomic details for many interactions but, to date, there has been limited discussion of how these two fields complement each other. Here, we apply a structural perspective to interpret interactions discovered by different techniques. This perspective reveals indirect interactions in two-hybrid systems, instances where molecular labels might obstruct interfaces, and possible explanations for why certain promiscuous proteins interact with many others. It also highlights that some methods favour tight complexes whereas others favour interactions of a more transient nature. We conclude by discussing how a combination of interaction discovery and structural biology will enhance our understanding of complex cellular processes.

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