2PQ3

N-Terminal Calmodulin Zn-Trapped Intermediate

Summary for 2PQ3

• Entry DOI: 10.2210/pdb2pq3/pdb
• Descriptor: Calmodulin, CACODYLATE ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: calmodulin, helix-turn-helix, ef-hand, n-terminal calmodulin, cam, n-cam, metal binding protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62161
• Total number of polymer chains: 1
• Total formula weight: 8722.16

Authors

Warren, J.T.,Guo, Q.,Tang, W.J. (deposition date: 2007-05-01, release date: 2007-10-16, Last modification date: 2024-02-21)

Primary citation

Warren, J.T.,Guo, Q.,Tang, W.J.
A 1.3-A structure of zinc-bound N-terminal domain of calmodulin elucidates potential early ion-binding step.
J.Mol.Biol., 374:517-527, 2007

PubMed 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.

PubMed: 17942116
DOI: 10.1016/j.jmb.2007.09.048

Experimental method

X-RAY DIFFRACTION (1.3 Å)