Functional dynamics of human FKBP12 revealed by methyl 13C rotating frame relaxation dispersion NMR spectroscopy

Journal of the American Chemical Society
Ulrika BrathFrans A A Mulder

Abstract

Transverse relaxation dispersion NMR spectroscopy can provide atom-specific information about time scales, populations, and the extent of structural reorganization in proteins under equilibrium conditions. A method is described that uses side-chain methyl groups as local reporters for conformational transitions taking place in the microsecond regime. The experiment measures carbon nuclear spin relaxation rates in the presence of continuous wave off-resonance irradiation, in proteins uniformly enriched with 13C, and partially randomly labeled with 2H. The method was applied to human FK-506 binding protein (FKBP12), which uses a common surface for binding substrates in its dual role as both an immunophilin and folding assistant. Conformational dynamics on a time scale of approximately 130 micros were detected for methyl groups located in the substrate binding pocket, demonstrating its plasticity in the absence of substrate. The spatial arrangement of affected side-chain atoms suggests that substrate recognition involves the rapid relative movement of the subdomain comprising residues Ala81-Thr96 and that the observed dynamics play an important role in facilitating the interaction of this protein with its many partners, including ...Continue Reading

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Citations

Aug 5, 2009·Journal of Biomolecular NMR·Christophe FarèsChristian Griesinger
Dec 4, 2009·Journal of Biomolecular NMR·Chenyun Guo, Vitali Tugarinov
Aug 2, 2013·Journal of Biomolecular NMR·Ulrich WeiningerPatrik Lundström
Sep 30, 2009·Chemical Reviews·Ivet BaharIndira H Shrivastava
Jul 22, 2008·Nature Chemical Biology·Nina M Goodey, Stephen J Benkovic
Apr 25, 2008·The Journal of Chemical Physics·Daniel S Weaver, Erik R P Zuiderweg
Nov 13, 2015·Biochemistry·Chun-Jiun YangMasatsune Kainosho
Aug 26, 2006·Molecular Microbiology·Gunter Fischer, Stephan Wawra
May 22, 2013·The Biochemical Journal·Sourajit M MustafiGriselda Hernández
May 18, 2016·The Journal of Chemical Physics·Arieh Warshel, Ram Prasad Bora
Oct 14, 2016·Journal of Biomolecular NMR·Griselda Hernández, David M LeMaster
Dec 13, 2016·Biochemistry·Ulrich WeiningerMikael Akke
Apr 23, 2014·The Biochemical Journal·Sourajit M MustafiGriselda Hernández
May 26, 2009·Chembiochem : a European Journal of Chemical Biology·Frans A A Mulder
Mar 5, 2020·Progress in Nuclear Magnetic Resonance Spectroscopy·Stefan Schütz, Remco Sprangers
Mar 19, 2020·Biochemical and Biophysical Research Communications·Qamar BashirGriselda Hernández
Sep 5, 2020·Progress in Nuclear Magnetic Resonance Spectroscopy·Iva PritišanacPeter Güntert
Feb 13, 2010·Journal of the American Chemical Society·Renee OttenFrans A A Mulder
Nov 4, 2008·Journal of the American Chemical Society·Raphaël PaquinGeoffrey Bodenhausen
Dec 21, 2006·Accounts of Chemical Research·Marco FragaiGiacomo Parigi
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Mar 21, 2013·Journal of the American Chemical Society·Jia-Ying GuanGregg Siegal
Aug 25, 2021·Journal of the American Chemical Society·Xinyao XiangRafael Brüschweiler

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