Molecular recognition of the disordered dihydropyridine receptor II-III loop by a conserved spry domain of the type 1 ryanodine receptor

Han -Shen Tae, Nicole C Norris, Yanfang Cui, Yamuna Karunasekara, Philip G Board, Angela F Dulhunty, Marco G Casarotto

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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.
Original languageEnglish
Pages (from-to)346 - 349
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Volume36
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

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