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.