title: Molecular recognition of the disordered dihydropyridine receptor II-III loop by a conserved spry domain of the type 1 ryanodine receptor.
abstract: 1. The dihydropyridine receptor (DHPR) II-III loop is an intrinsically unstructured region made up of alpha-helical and beta-turn secondary structure elements with the N and C termini in close spatial proximity. 2. The DHPR II-III loop interacts in vitro with a ryanodine receptor (RyR) 1 SPRY domain through alpha-helical segments located in the A and B regions. Mutations within the A and B regions in the DHPR II-III loop alter the binding affinity to the SPRY2 domain. 3. The A and C peptides derived from DHPR II-III loop show negative cooperativity in binding to the SPRY2 domain. 4. The SPRY2 domain of the RyR1 (1085-1208) forms a beta-sheet sandwich structure flanked by variable loop regions. An acidic loop region of SPRY2 (1107-1121) forms part of a negatively charged cleft that is implicated in the binding of the DHPR II-III loop. 5. The mutant E1108A located in the negatively charged loop of SPRY2 reduces the binding affinity to the DHPR II-III loop.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Han-Shen
authors.initials: HS
authors.lastname: Tae
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Norris
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Cui
authors.forename: Yamuna
authors.initials: Y
authors.lastname: Karunasekara
authors.forename: Philip G
authors.initials: PG
authors.lastname: Board
authors.forename: Angela F
authors.initials: AF
authors.lastname: Dulhunty
authors.forename: Marco G
authors.initials: MG
authors.lastname: Casarotto
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel