TY - JOUR
T1 - Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP
T2 - A Comparison with Amylin
AU - Sizemore, Sara M.
AU - Cope, Stephanie M.
AU - Roy, Anindya
AU - Ghirlanda, Giovanna
AU - Vaiana, Sara
N1 - Publisher Copyright:
© 2015 Biophysical Society.
PY - 2015/9/2
Y1 - 2015/9/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bpj.2015.07.023
DO - 10.1016/j.bpj.2015.07.023
M3 - Article
C2 - 26331261
AN - SCOPUS:84940538951
SN - 0006-3495
VL - 109
SP - 1038
EP - 1048
JO - Biophysical journal
JF - Biophysical journal
IS - 5
ER -