Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP: A Comparison with Amylin

Biophysical Journal
Sara M SizemoreSara M Vaiana

Abstract

We provide the first direct experimental comparison, to our knowledge, between the internal dynamics of calcitonin-gene-related peptide (CGRP) and amylin (islet amyloid polypeptide, IAPP), two intrinsically disordered proteins of the calcitonin peptide family. Our end-to-end contact formation measurements reveal that in aqueous solution (i.e., in the absence of structure-inducing organic solvents) CGRP preferentially populates conformations with short end-to-end distances. However, the end-to-end distance of CGRP is larger than that of IAPP. We find that electrostatic interactions can account for such a difference. At variance with previous reports on the secondary structure of CGRP, we find that the end-to-end distance of the peptide increases with decreasing pH and salt concentration, due to Coulomb repulsion by charged residues. Interestingly, our data show that the reconfiguration dynamics of CGRP is significantly slower than that of human IAPP in water but not in denaturant, providing experimental evidence for roughness in the energy landscape, or internal friction, in these peptides. The data reported here provide both structural and dynamical information that can be used to validate results from molecular simulations of ...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A N RobertsE A Foot
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R Zwanzig
Feb 13, 1986·Biochemical and Biophysical Research Communications·J R TippinsI MacIntyre
Nov 14, 1986·Biochemical and Biophysical Research Communications·P WestermarkK Sletten
Jan 3, 1985·Nature·S D BrainI MacIntyre
May 5, 1982·Journal of Molecular Biology·J Kyte, R F Doolittle
Apr 7, 1999·Journal of Molecular Biology·R KayedA Kapurniotu
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·L J LapidusJ Hofrichter
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·B A ShoemakerP G Wolynes
Sep 11, 2002·Neurology·Hayrunnisa Bolay, Michael A Moskowitz
Feb 11, 2003·Trends in Biochemical Sciences·Kannan GunasekaranRuth Nussinov
Feb 26, 2004·Biochemistry·Huan-Xiang Zhou
Mar 12, 2004·The New England Journal of Medicine·Jes OlesenUNKNOWN BIBN 4096 BS Clinical Proof of Concept Study Group
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jonathan E KohnKevin W Plaxco
Sep 29, 2004·Biochemistry·Suzette A PabitStephen J Hagen
Aug 3, 2005·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Daniela Pietrobon
Apr 18, 2006·Biophysical Journal·Marco BuscagliaJames Hofrichter
Jun 29, 2006·Physical Review Letters·Robert B Best, Gerhard Hummer
Aug 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Andreas MöglichThomas Kiefhaber
Nov 25, 2006·Protein Science : a Publication of the Protein Society·Jessica A Williamson, Andrew D Miranker
Jan 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kusai A MerchantWilliam A Eaton
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Daniel NettelsBenjamin Schuler
Mar 14, 2007·Biochimica Et Biophysica Acta·Sajith A Jayasinghe, Ralf Langen
Apr 12, 2008·PLoS Computational Biology·Adrian Gustavo TurjanskiGerhard Hummer
Nov 8, 2008·Biochemistry·Ravi Prakash Reddy NangaAyyalusamy Ramamoorthy
Dec 17, 2008·Physical Chemistry Chemical Physics : PCCP·Guy ZivGilad Haran
Jan 23, 2009·Current Opinion in Structural Biology·Peter E Wright, H Jane Dyson
May 22, 2009·Journal of the American Chemical Society·Ravi Prakash Reddy NangaAyyalusamy Ramamoorthy
Aug 4, 2009·Journal of Molecular Biology·Jessica A WilliamsonAndrew D Miranker
Nov 26, 2009·The Journal of Chemical Physics·Feng LiuMartin Gruebele
Dec 2, 2009·Biophysical Journal·Sara M VaianaJames Hofrichter

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Citations

May 26, 2017·PloS One·Chamani NiyangodaMartin Muschol
Apr 2, 2018·The Journal of Chemical Physics·Taylor Firman, Kingshuk Ghosh
Feb 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Andrea SorannoBenjamin Schuler
Sep 2, 2020·International Journal of Molecular Sciences·Greta BianchiStefania Brocca
Mar 8, 2020·Archives of Biochemistry and Biophysics·Andrea Soranno
Mar 11, 2021·The Journal of Physical Chemistry. B·Chenliang XiaWei Wang
Jan 11, 2018·Chemical Reviews·Huan-Xiang Zhou, Xiaodong Pang
Sep 15, 2018·The Journal of Physical Chemistry. B·Andrea SorannoMarco Buscaglia

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