Ultrabithorax, an Intrinsically Disordered Protein, Selects Protein Interactions by Topology

摘要: Interaction between two structured proteins requires both complementary topologies to generate a sufficient interface and surface groups capable of forming bonds within this stabilize the complex. When one (or both) partners is intrinsically disordered as monomer, but folds upon interaction, same rules for partner selection - topology chemistry are expected apply. However, many do not fold even when stable protein interactions, creating “fuzzy” complexes. In these cases, extreme instability may preclude well-defined interface. Despite apparent lack constraints, specifically reliably select correct in vivo. To understand that determine fuzzy complexes, we have evaluated interactions formed by Drosophila melanogaster Hox transcription factor Ultrabithorax (Ubx). Ubx interacts vitro with 29 other proteins. All require regions Ubx. Surprisingly, despite structure regions, appears topology: 22 include five out nearly 1200 listed SCOP. These data suggest remains constraint Although some bind equally well large Ubx, clearly prefer binding alternatively spliced microexons. Partners preferring microexon region various splicing isoforms differentially. Consequently, likely important interactions. Together, our suggests key criteria selection,