Catching Functional Modes and Structural Communication in Dbl Family Rho Guanine Nucleotide Exchange Factors

Journal of Chemical Information and Modeling
Francesco RaimondiFrancesca Fanelli

Abstract

Computational approaches such as Principal Component Analysis (PCA) and Elastic Network Model-Normal Mode Analysis (ENM-NMA) are proving to be of great value in investigating relevant biological problems linked to slow motions with no demand in computer power. In this study, these approaches have been coupled to the graph theory-based Protein Structure Network (PSN) analysis to dissect functional dynamics and structural communication in the Dbl family of Rho Guanine Nucleotide Exchange Factors (RhoGEFs). They are multidomain proteins whose common structural feature is a DH-PH tandem domain deputed to the GEF activity that makes them play a central role in cell and cancer biology. While their common GEF action is accomplished by the DH domain, their regulatory mechanisms are highly variegate and depend on the PH and the additional domains as well as on interacting proteins. Major evolutionary-driven deformations as inferred from PCA concern the α6 helix of DH that dictates the orientation of the PH domain. Such deformations seem to depend on the mechanisms adopted by the GEF to prevent Rho binding, i.e. functional specialization linked to autoinhibition. In line with PCA, ENM-NMA indicates α6 and the linked PH domain as the port...Continue Reading

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Citations

Dec 22, 2016·Journal of Chemical Theory and Computation·Angelo FellineFrancesca Fanelli
Mar 10, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guang HuMattia Falconi
Sep 13, 2017·Cold Spring Harbor Perspectives in Biology·Vania Braga
Apr 20, 2019·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Jie YanHuixia Yang
Apr 14, 2016·Biochemical Society Transactions·Francesca FanelliMichele Seeber
May 31, 2019·Nucleic Acids Research·Gurdeep SinghFrancesco Raimondi
Dec 14, 2018·International Journal of Molecular Sciences·Pontus Aspenström
Sep 7, 2019·Journal of Chemical Information and Modeling·Angelo FellineFrancesca Fanelli

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