3UCT

Structure of Mn2+-bound N-terminal domain of calmodulin in the presence of Zn2+

Summary for 3UCT

• Entry DOI: 10.2210/pdb3uct/pdb
• Related: 3UCW 3UCY
• Descriptor: Calmodulin, MANGANESE (II) ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: ef-hand, metal binding, calcium regulation, calcium-binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62158
• Total number of polymer chains: 2
• Total formula weight: 18190.71

Authors

Senguen, F.T.,Grabarek, Z. (deposition date: 2011-10-27, release date: 2012-08-08, Last modification date: 2024-02-28)

Primary citation

Senguen, F.T.,Grabarek, Z.
X-ray Structures of Magnesium and Manganese Complexes with the N-Terminal Domain of Calmodulin: Insights into the Mechanism and Specificity of Metal Ion Binding to an EF-Hand.
Biochemistry, 51:6182-6194, 2012

PubMed Abstract: Calmodulin (CaM), a member of the EF-hand superfamily, regulates many aspects of cell function by responding specifically to micromolar concentrations of Ca(2+) in the presence of an ~1000-fold higher concentration of cellular Mg(2+). To explain the structural basis of metal ion binding specificity, we have determined the X-ray structures of the N-terminal domain of calmodulin (N-CaM) in complexes with Mg(2+), Mn(2+), and Zn(2+). In contrast to Ca(2+), which induces domain opening in CaM, octahedrally coordinated Mg(2+) and Mn(2+) stabilize the closed-domain, apo-like conformation, while tetrahedrally coordinated Zn(2+) ions bind at the protein surface and do not compete with Ca(2+). The relative positions of bound Mg(2+) and Mn(2+) within the EF-hand loops are similar to those of Ca(2+); however, the Glu side chain at position 12 of the loop, whose bidentate interaction with Ca(2+) is critical for domain opening, does not bind directly to either Mn(2+) or Mg(2+), and the vacant ligand position is occupied by a water molecule. We conclude that this critical interaction is prevented by specific stereochemical constraints imposed on the ligands by the EF-hand β-scaffold. The structures suggest that Mg(2+) contributes to the switching off of calmodulin activity and possibly other EF-hand proteins at the resting levels of Ca(2+). The Mg(2+)-bound N-CaM structure also provides a unique view of a transiently bound hydrated metal ion and suggests a role for the hydration water in the metal-induced conformational change.

PubMed: 22803592
DOI: 10.1021/bi300698h

Experimental method

X-RAY DIFFRACTION (1.9 Å)