Deciphering the deformation modes associated with function retention and specialization in members of the Ras superfamily.

TitleDeciphering the deformation modes associated with function retention and specialization in members of the Ras superfamily.
Publication TypeJournal Article
Year of Publication2010
AuthorsRaimondi, Francesco, Orozco Modesto, and Fanelli Francesca
JournalStructure
Volume18
Pagination402-14
Date Published2010 Mar 10
ISSN1878-4186
KeywordsAmino Acid Sequence, Evolution, Models, Molecular, Molecular Sequence Data, Principal Component Analysis, ras Proteins
Abstract

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 information encrypted into the conserved core and to separate the trans-family intrinsic flexibility associated 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 deformation 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 functional specialization when associated with evolution-driven deformations of protein portions essentially 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.

DOI10.1016/j.str.2009.12.015
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