3RV5

Crystal structure of human cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid

Summary for 3RV5

• Entry DOI: 10.2210/pdb3rv5/pdb
• Related: 1AP4 1J1D 1LXF 1MXL 1SPY 1WRK
• Descriptor: Troponin C, slow skeletal and cardiac muscles, CADMIUM ION, (3ALPHA,5BETA,12ALPHA)-3,12-DIHYDROXYCHOLAN-24-OIC ACID, ... (5 entities in total)
• Functional Keywords: helix-loop-helix ef-hand motif, metal ion coordination, calcium sensor, contractile protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 46038.00

Authors

Li, A.Y.,Lee, J.,Borek, D.,Otwinowski, Z.,Tibbits, G.,Paetzel, M. (deposition date: 2011-05-06, release date: 2011-08-31, Last modification date: 2024-10-16)

Primary citation

Li, A.Y.,Lee, J.,Borek, D.,Otwinowski, Z.,Tibbits, G.F.,Paetzel, M.
Crystal structure of cardiac troponin C regulatory domain in complex with cadmium and deoxycholic Acid reveals novel conformation.
J.Mol.Biol., 413:699-711, 2011

PubMed Abstract: The amino-terminal regulatory domain of cardiac troponin C (cNTnC) plays an important role as the calcium sensor for the troponin complex. Calcium binding to cNTnC results in conformational changes that trigger a cascade of events that lead to cardiac muscle contraction. The cardiac N-terminal domain of TnC consists of two EF-hand calcium binding motifs, one of which is dysfunctional in binding calcium. Nevertheless, the defunct EF-hand still maintains a role in cNTnC function. For its structural analysis by X-ray crystallography, human cNTnC with the wild-type primary sequence was crystallized under a novel crystallization condition. The crystal structure was solved by the single-wavelength anomalous dispersion method and refined to 2.2 Å resolution. The structure displays several novel features. Firstly, both EF-hand motifs coordinate cadmium ions derived from the crystallization milieu. Secondly, the ion coordination in the defunct EF-hand motif accompanies unusual changes in the protein conformation. Thirdly, deoxycholic acid, also derived from the crystallization milieu, is bound in the central hydrophobic cavity. This is reminiscent of the interactions observed for cardiac calcium sensitizer drugs that bind to the same core region and maintain the "open" conformational state of calcium-bound cNTnC. The cadmium ion coordination in the defunct EF-hand indicates that this vestigial calcium binding site retains the structural and functional elements that allow it to coordinate a cadmium ion. However, it is a result of, or concomitant with, large and unusual structural changes in cNTnC.

PubMed: 21920370
DOI: 10.1016/j.jmb.2011.08.049

Experimental method

X-RAY DIFFRACTION (2.2 Å)