Molecular basis for Rac1 recognition by guanine nucleotide exchange factors.
作者： Antoine E. Karnoub , David K. Worthylake , Kent L. Rossman , Wendy Morse Pruitt , Sharon L. Campbell
DOI: 10.1038/NSB719
关键词:
摘要: Rho GTPases are activated by a family of guanine nucleotide exchange factors (GEFs) known as Dbl proteins. The structural basis for how GEFs recognize and activate is presently ill defined. Here, we utilized the crystal structure DH/PH domains Rac-specific GEF Tiam1 in complex with Rac1 to determine elements that regulate specificity this interaction. We show residues beta2-beta3 region critical recognition. Additionally, determined single Rac1-to-Cdc42 mutation (W56F) was sufficient abolish sensitivity allow recognition Cdc42-specific Intersectin while not impairing downstream activities. Our findings identified unique determinants provide important insights into mechanism selection GTPase targets.
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