Document Type
Article
Publication Date
2015
Keywords
Intrinsically disordered protein, caldesmon, calmodulin, protein-protein interaction, MoRF
Digital Object Identifier (DOI)
https://doi.org/10.7287/peerj.preprints.1261v1
Abstract
We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636-771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136 and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136 with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136 tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be described as the “buttons on a charged string” model, where the electrostatic attraction between the intrinsically disordered CaD136 and the CaM is solidified in a “snapping buttons” manner by specific packing of the CaD136 “pliable buttons” (which are the short segments of fluctuating local structure condensed around the tryptophan residues) at the CaD136-CaM interface. Our data also show that all three “buttons” are important for binding, since mutation of any of the tryptophans affects CaD136-CaM binding and since CaD136 remains CaM-buttoned even when two of the three tryptophans are mutated to alanines.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
PeerJ, v. 3, art. e1261v1
Scholar Commons Citation
Permyakov, Sergei E.; Permyakov, Eugene A.; and Uversky, Vladimir N., "Does Intrinsically Disordered Caldesmon Bind Calmodulin via the “Buttons on a String” Mechanism?" (2015). Molecular Medicine Faculty Publications. 45.
https://digitalcommons.usf.edu/mme_facpub/45
