MOLECULAR RECOGNITION OF THE DISORDERED DIHYDROPYRIDINE RECEPTOR II-III LOOP BY A CONSERVED SPRY DOMAIN OF THE TYPE 1 RYANODINE RECEPTOR

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

Source: Clinical and Experimental Pharmacology and Physiology, Volume 36, Number 3, March 2009 , pp. 346-349(4)

Publisher: Wiley-Blackwell

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Abstract:

SUMMARY

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The dihydropyridine receptor (DHPR) II-III loop is an intrinsically unstructured region made up of α-helical and β-turn secondary structure elements with the N and C termini in close spatial proximity.

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The DHPR II-III loop interacts in vitro with a ryanodine receptor (RyR) 1 SPRY domain through α-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.

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The A and C peptides derived from DHPR II-III loop show negative cooperativity in binding to the SPRY2 domain.

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The SPRY2 domain of the RyR1 (1085-1208) forms a β-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.

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The mutant E1108A located in the negatively charged loop of SPRY2 reduces the binding affinity to the DHPR II-III loop.

Keywords: dihydropyridine receptor; II-III loop; nuclear magnetic resonance; protein-protein interaction; ryanodine receptor

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1440-1681.2008.05130.x

Publication date: 2009-03-01