2pq3
N-Terminal Calmodulin Zn-Trapped Intermediate
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OverviewOverview
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.
About this StructureAbout this Structure
2PQ3 is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
A 1.3-A structure of zinc-bound N-terminal domain of calmodulin elucidates potential early ion-binding step., Warren JT, Guo Q, Tang WJ, J Mol Biol. 2007 Nov 23;374(2):517-27. Epub 2007 Sep 21. PMID:17942116
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