Slow Internal Dynamics and Charge Expansion in the Disordered Protein CGRP: A Comparison with Amylin.
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.
Center for Biological Physics, Arizona State University, Tempe, Arizona; Department of Physics, Arizona State University, Tempe, Arizona.
Sara M
SM
Sizemore
Center for Biological Physics, Arizona State University, Tempe, Arizona; Department of Physics, Arizona State University, Tempe, Arizona.
Stephanie M
SM
Cope
Department of Biochemistry, Molecular Engineering and Sciences, University of Washington, Seattle, Washington.
Anindya
A
Roy
Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona.
Giovanna
G
Ghirlanda
Center for Biological Physics, Arizona State University, Tempe, Arizona; Department of Physics, Arizona State University, Tempe, Arizona. Electronic address: sara.vaiana@asu.edu.
Sara M
SM
Vaiana
D000595:Amino Acid Sequence; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055672:Static Electricity
D064267:Intrinsically Disordered Proteins; D058228:Islet Amyloid Polypeptide; D015740:Calcitonin Gene-Related Peptide