Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP

A Comparison with Amylin

Sara M. Sizemore, Stephanie M. Cope, Anindya Roy, Giovanna Ghirlanda, Sara M. Vaiana

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 calcitonin family peptides in aqueous solution.

Original languageEnglish
Pages (from-to)1038-1048
Number of pages11
JournalBiophysical Journal
Volume109
Issue number5
DOIs
Publication statusPublished - Sep 2 2015

Fingerprint

Islet Amyloid Polypeptide
Calcitonin Gene-Related Peptide
Peptides
Calcitonin
Proteins
Intrinsically Disordered Proteins
Friction
Static Electricity
Salts
peptide A
Water

ASJC Scopus subject areas

  • Biophysics

Cite this

Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP : A Comparison with Amylin. / Sizemore, Sara M.; Cope, Stephanie M.; Roy, Anindya; Ghirlanda, Giovanna; Vaiana, Sara M.

In: Biophysical Journal, Vol. 109, No. 5, 02.09.2015, p. 1038-1048.

Research output: Contribution to journalArticle

Sizemore, Sara M. ; Cope, Stephanie M. ; Roy, Anindya ; Ghirlanda, Giovanna ; Vaiana, Sara M. / Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP : A Comparison with Amylin. In: Biophysical Journal. 2015 ; Vol. 109, No. 5. pp. 1038-1048.
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