title: Intrinsically disordered caldesmon binds calmodulin via the "buttons on a string" mechanism.
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.
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation, Russian Academy of Sciences , Pushchino, Moscow Region , Russia.
authors.forename: Sergei E
authors.initials: SE
authors.lastname: Permyakov
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation, Russian Academy of Sciences , Pushchino, Moscow Region , Russia.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Permyakov
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation, Russian Academy of Sciences , Pushchino, Moscow Region , Russia ; Department of Molecular Medicine, University of South Florida , Tampa, FL , USA.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
keywords: Caldesmon; Calmodulin; Intrinsically disordered protein; Molecular Recognition Feature (MoRF).; Protein–protein interaction