3IM6

Crystal structure of mouse Ryanodine Receptor 2 mutant V186M

Summary for 3IM6

• Entry DOI: 10.2210/pdb3im6/pdb
• Related: 3ILA 3IM5 3IM7
• Descriptor: Cardiac Ca2+ release channel, SULFATE ION (3 entities in total)
• Functional Keywords: ryanodine receptor 2, calcium release channel, ion channel, arrhythmia, cpvt, arvd2, arvc2, disease mutation, ion transport, ionic channel, transmembrane, transport, signaling protein
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 24295.33

Authors

Van Petegem, F.,Lobo, P.A. (deposition date: 2009-08-09, release date: 2009-11-17, Last modification date: 2023-09-06)

Primary citation

Lobo, P.A.,Van Petegem, F.
Crystal structures of the N-terminal domains of cardiac and skeletal muscle ryanodine receptors: insights into disease mutations.
Structure, 17:1505-1514, 2009

PubMed Abstract: Ryanodine receptors (RyRs) are channels governing the release of Ca(2+) from the sarcoplasmic or endoplasmic reticulum. They are required for the contraction of both skeletal (RyR1) and cardiac (RyR2) muscles. Mutations in both RyR1 and RyR2 have been associated with severe genetic disorders, but high-resolution data describing the disease variants in detail have been lacking. Here we present the crystal structures of the N-terminal domains of both RyR2 (1-217) and RyR1 (9-205) at 2.55 A and 2.9 A, respectively. The domains map in a hot spot region for disease mutations. Both structures consist of a core beta trefoil domain flanked by an alpha helix. Crystal structures of two RyR2 disease mutants, A77V (2.2 A) and V186M (1.7 A), show that the mutations cause distinct local changes in the surface of the protein. A RyR2 deletion mutant causes significant changes in the thermal stability. The disease positions highlight two putative binding interfaces required for normal RyR function.

PubMed: 19913485
DOI: 10.1016/j.str.2009.08.016

Experimental method

X-RAY DIFFRACTION (1.7 Å)