Resolution of Site-Specific Conformational Heterogeneity in Proline-Rich Molecular Recognition by Src Homology 3 Domains

Journal of the American Chemical Society
Rachel E HornessMegan C Thielges

Abstract

Conformational heterogeneity and dynamics are increasingly evoked in models of protein molecular recognition but are challenging to experimentally characterize. Here we combine the inherent temporal resolution of infrared (IR) spectroscopy with the spatial resolution afforded by selective incorporation of carbon-deuterium (C-D) bonds, which provide frequency-resolved absorptions within a protein IR spectrum, to characterize the molecular recognition of the Src homology 3 (SH3) domain of the yeast protein Sho1 with its cognate proline-rich (PR) sequence of Pbs2. The IR absorptions of C-D bonds introduced at residues along a peptide of the Pbs2 PR sequence report on the changes in the local environments upon binding to the SH3 domain. Interestingly, upon forming the complex the IR spectra of the peptides labeled with C-D bonds at either of the two conserved prolines of the PXXP consensus recognition sequence show more absorptions than there are C-D bonds, providing evidence for the population of multiple states. In contrast, the NMR spectra of the peptides labeled with (13)C at the same residues show only single resonances, indicating rapid interconversion on the NMR time scale. Thus, the data suggest that the SH3 domain recogniz...Continue Reading

References

Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·J Foote, C Milstein
Feb 12, 1998·Science·T Pawson, J D Scott
Dec 2, 2000·Journal of Molecular Biology·F CordierL K Nicholson
Nov 8, 2001·Journal of Molecular Biology·C WangL K Nicholson
Apr 30, 2003·Protein Science : a Publication of the Protein Society·Josephine C Ferreon, Vincent J Hilser
Mar 18, 2004·Journal of the American Chemical Society·Laura B SagleFloyd E Romesberg
Feb 1, 1958·Proceedings of the National Academy of Sciences of the United States of America·D E Koshland
May 4, 2006·Journal of the American Chemical Society·Matthew E CremeensFloyd E Romesberg
Sep 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jörg ZimmermannFloyd E Romesberg
Dec 14, 2007·Nature·Katherine Henzler-Wildman, Dorothee Kern
Oct 21, 2009·Nature Chemical Biology·David D BoehrPeter E Wright
Nov 27, 2010·Current Opinion in Structural Biology·Shiou-Ru Tzeng, Charalampos G Kalodimos
Nov 15, 2012·Accounts of Chemical Research·Neal J Zondlo
Sep 17, 2014·Journal of the American Chemical Society·Ramkrishna AdhikaryFloyd E Romesberg
May 9, 2015·The Journal of Physical Chemistry. B·Edward J BasomMegan C Thielges

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Citations

May 27, 2017·Biochemistry·Ramkrishna AdhikaryFloyd E Romesberg
Sep 15, 2020·PLoS Computational Biology·Gabriella J GerlachK Aurelia Ball
Sep 8, 2016·Acta Crystallographica. Section F, Structural Biology Communications·Ana Camara-ArtigasJose Manuel Martin-Garcia
Nov 22, 2018·Analytical Chemistry·Gregory S Bukowski, Megan C Thielges
Sep 20, 2019·The Journal of Physical Chemistry. B·Gregory S BukowskiMegan C Thielges
Mar 9, 2019·The Journal of Physical Chemistry. B·Sashary Ramos, Megan C Thielges
Oct 23, 2018·The Journal of Physical Chemistry. B·Claudio ZanobiniGerhard Stock

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