Natively unfolded C-terminal domain of caldesmon remains substantially unstructured after the effective binding to calmodulin

The structure of C-terminal do- main (CaD136, C-terminal residues 636 -771) of chicken gizzard caldesmon has been analyzed by a variety of physico-chemical methods. We are show- ing here that CaD136 does not have globular struc- ture, has low secondary structure content, is essen- tially noncompact, as it follows from high Rg and RS values, and is characterized by the absence of dis- tinct heat absorption peaks, i.e. it belongs to the family of natively unfolded (or intrinsically unstruc- tured) proteins. Surprisingly, effective binding of single calmodulin molecule (Kd 1.4 0.2 M) leads only to a very moderate folding of this protein and CaD136 remains substantially unfolded within its tight complex with calmodulin. The biological sig- nificance of these observations is discussed. Proteins