♦ See referenced article, J. Biol. Chem. 2013, 288, 4486–4500
The diffuse B-cell lymphoma (Dbl) family of guanine nucleotide exchange factors (GEFs) directly activates the proteins of the Rho family. Rho proteins are critical to numerous fundamental and specialized cellular processes. However, the complexity of interactions among 74 Dbl- and 25 Rho-related proteins in humans has not been systematically explored so far. In this Paper of the Week, a team led by Mohammad Reza Ahmadian at the Heinrich-Heine University in Germany described their meta-analysis of the sequence-structure-function-property relationships between 21 representative Dbl and 12 Rho proteins. Among other things, the investigators identified hot spots and fingerprints determining selective Dbl-Rho protein interactions, classified Dbl family members according to their catalytic efficiencies and substrate selectivity, and found that not all Rho proteins require GEFs like Dbl proteins. The authors claim that the performed meta-analysis and classification of the Dbl family into distinct subfamilies open doors to further systems biology-oriented and cell-based research.
The Venn diagram shows the subdivision of the Dbl family proteins based on their substrate selection (16 Rho, 19 Cdc42, 11 Rac, 5 Rho/Cdc42, and 6 Rho/Cdc42/Rac).