title: Physical coupling between ryanodine receptor-calcium release channels.
abstract: Ryanodine receptor-calcium release channels play a pivotal role in the calcium signaling that mediates muscle excitation-contraction coupling. Their membrane organization into regular patterns, functional gating studies and theoretical analysis of receptor clustering have led to models that invoke allosteric interaction between individual channel oligomers as a critical mechanism for control of calcium release. Here we show that in reconstituted "checkerboard-like" lattices that mimic in situ membrane channel arrays, each oligomer is interlocked physically with four adjacent oligomers via a specific domain-domain interaction. Direct physical coupling between ryanodine receptors provides structural evidence for an inter-oligomer allosteric mechanism in channel regulation. Therefore, in addition to established cytosolic and luminal regulation of function, these observations indicate that channel-channel communication through physical coupling provides a novel mode of regulation of intracellular calcium release channels.
authors.affiliation: Department of Biophysics, Peking University Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100083, China. ccyin@bjmu.edu.cn
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Yin
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Blayney
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Lai
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel