2R28
The complex Structure of Calmodulin Bound to a Calcineurin Peptide
Summary for 2R28
| Entry DOI | 10.2210/pdb2r28/pdb |
| Descriptor | Calmodulin, Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | protein-peptide complex, acetylation, calcium, methylation, phosphorylation, ubl conjugation, alternative splicing, calmodulin-binding, hydrolase, iron, metal-binding, nucleus, protein phosphatase, zinc, metal binding protein-hydrolase complex, metal binding protein/hydrolase |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cytoplasm, cytoskeleton, spindle: P62158 Nucleus (By similarity): Q08209 |
| Total number of polymer chains | 4 |
| Total formula weight | 39636.63 |
| Authors | |
| Primary citation | Ye, Q.,Wang, H.,Zheng, J.,Wei, Q.,Jia, Z. The complex structure of calmodulin bound to a calcineurin peptide. Proteins, 73:19-27, 2008 Cited by PubMed Abstract: The activity of the protein phosphatase calcineurin (CN) is regulated by an autoinhibition mechanism wherein several domains from its catalytic A subunit, including the calmodulin binding domain (CaMBD), block access to its active site. Upon binding of Ca2+ and calmodulin (Ca2+/CaM) to CaMBD, the autoinhibitory domains dissociate from the catalytic groove, thus activating the enzyme. To date, the structure of the CN/CaM/Ca2+ complex has not been determined in its entirety. Previously, we determined the structure of a fusion protein consisting of CaM and a 25-residue peptide taken from the CaMBD, joined by a 5-glycine linker. This structure revealed a novel CaM binding motif. However, the presence of the extraneous glycine linker cast doubt on the authenticity of this structure as an accurate representation of CN/CaM binding in vivo. Thus, here, we have determined the crystal structure of CaM complexed with the 25-residue CaMBD peptide without the glycine linker at a resolution of 2.1 A. The structure is essentially identical to the fusion construction which displays CaM bound to the CaMBD peptide as a dimer with an open, elongated conformation. The N-lobe from one molecule and C-lobe from another encompass and bind the CaMBD peptide. Thus, it validates the existence of this novel CaM binding motif. Our experiments suggest that the dimeric CaM/CaMBD complex exists in solution, which is unambiguously validated using a carefully-designed CaM-sepharose pull-down experiment. We discuss structural features that produce this novel binding motif, including the role of the CaMBD peptide residues Arg-408, Val-409, and Phe-410, which work to provide rigidity to the otherwise flexible central CaM helix joining the N- and C-lobes, ultimately keeping these lobes apart and forcing "head-to-tail" dimerization to attain the requisite N- and C-lobe pairing for CaMBD binding. PubMed: 18384083DOI: 10.1002/prot.22032 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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