Deciphering the Deformation Modes Associated with Function Retention and Specialization in Members of the Ras Superfamily – Structure, 2010

Francesco Raimondi, Modesto Orozco, and Francesca Fanelli

SUMMARY

The evolutionary and physical deformability patterns of members of the Ras GTPase superfamily were investigated by Principal Component and Elastic Network-Normal Mode analyses.

The study helped to decipher the dynamics infor- mation encrypted into the conserved core and to separate the trans-family intrinsic flexibility associ- ated with a common function from the protein motions related to functional specialization of selected families or family members. The conserved core is dynamically divided into two lobes. The defor- mation modes, which allow the Ras GTPases to accomplish their switching function, are conserved along evolution and are localized in lobe 1 portions close to the nucleotide. These modes lead to func- tional specialization when associated with evolu- tion-driven deformations of protein portions essen- tially located in lobe 2, distal from the nucleotide, and involved in peculiar interactions with membrane, guanine nucleotide exchange factors, or effectors.

Overall, a complete picture of the functional and evolutionary dynamics of the Ras superfamily emerges.

Structure 18, 402–414, March 10, 2010 PMID: 20223222