Analysis of 15N鈥?sup>1H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond鈥揘anosecond Dynamics of the Rho GTPase Binding Doma

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• 作者：Mirco Zerbetto ; Ross Anderson ; Sabine Bouguet-Bonnet ; Mariano Rech ; Liqun Zhang ; Eva Meirovitch ; Antonino Polimeno ; Matthias Buck
• 刊名：The Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：January 10, 2013
• 年：2013
• 卷：117
• 期：1
• 页码：174-184
• 全文大小：485K
• 年卷期：v.117,no.1(January 10, 2013)
• ISSN：1520-5207

文摘

We investigate picosecond鈥搉anosecond dynamics of the Rho-GTPase Binding Domain (RBD) of plexin-B1, which plays a key role in plexin-mediated cell signaling. Backbone ¹⁵N relaxation data of the dimeric RBD are analyzed with the model-free (MF) method, and with the slowly relaxing local structure/molecular dynamics (SRLS-MD) approach. Independent analysis of the MD trajectories, based on the MF paradigm, is also carried out. MF is a widely popular and simple method, SRLS is a general approach, and SRLS-MD is an integrated approach we developed recently. Corresponding parameters from the RBD dimer, a previously studied RBD monomer mutant, and the previously studied complex of the latter with the GTPase Rac1, are compared. The L₂, L₃, and L₄ loops of the plexin-B1 RBD are involved in interactions with other plexin domains, GTPase binding, and RBD dimerization, respectively. Peptide groups in the loops of both the monomeric and dimeric RBD are found to experience weak and moderately asymmetric local ordering centered approximately at the C_i鈥?^伪鈥揅_i^伪 axes, and nanosecond backbone motion. Peptide groups in the 伪-helices and the 尾-strands of the dimer (the 尾-strands of the monomer) experience strong and highly asymmetric local ordering centered approximately at the C_i鈥?^伪鈥揅_i^伪 axes (N鈥揌 bonds). N鈥揌 fluctuations occur on the picosecond time scale. An allosteric pathway for GTPase binding, providing new insights into plexin function, is delineated.