Unknown

Dataset Information

0

A 1.3-A structure of zinc-bound N-terminal domain of calmodulin elucidates potential early ion-binding step.


ABSTRACT: Calmodulin (CaM) is a 16.8-kDa calcium-binding protein involved in calcium-signal transduction. It is the canonical member of the EF-hand family of proteins, which are characterized by a helix-loop-helix calcium-binding motif. CaM is composed of N- and C-terminal globular domains (N-CaM and C-CaM), and within each domain there are two EF-hand motifs. Upon binding calcium, CaM undergoes a significant, global conformational change involving reorientation of the four helix bundles in each of its two domains. This conformational change upon ion binding is a key component of the signal transduction and regulatory roles of CaM, yet the precise nature of this transition is still unclear. Here, we present a 1.3-A structure of zinc-bound N-terminal calmodulin (N-CaM) solved by single-wavelength anomalous diffraction phasing of a selenomethionyl N-CaM. Our zinc-bound N-CaM structure differs from previously reported CaM structures and resembles calcium-free apo-calmodulin (apo-CaM), despite the zinc binding to both EF-hand motifs. Structural comparison with calcium-free apo-CaM, calcium-loaded CaM, and a cross-linked calcium-loaded CaM suggests that our zinc-bound N-CaM reveals an intermediate step in the initiation of metal ion binding at the first EF-hand motif. Our data also suggest that metal ion coordination by two key residues in the first metal-binding site represents an initial step in the conformational transition induced by metal binding. This is followed by reordering of the N-terminal region of the helix exiting from this first binding loop. This conformational switch should be incorporated into models of either stepwise conformational transition or flexible, dynamic energetic state sampling-based transition.

PROVIDER: S-EPMC2128742 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC3081547 | BioStudies
| S-EPMC3360750 | BioStudies
| S-EPMC8491939 | BioStudies
| S-EPMC3448793 | BioStudies
| S-EPMC554124 | BioStudies
| S-EPMC6561220 | BioStudies
| S-EPMC1450128 | BioStudies
| S-EPMC3042556 | BioStudies
| S-EPMC3516504 | BioStudies
| S-EPMC3145654 | BioStudies