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MOLECULAR RECOGNITION OF THE DISORDERED DIHYDROPYRIDINE RECEPTOR II–III LOOP BY A CONSERVED SPRY DOMAIN OF THE TYPE 1 RYANODINE RECEPTOR
Author(s) -
Tae HanShen,
Norris Nicole C,
Cui Yanfang,
Karunasekara Yamuna,
Board Philip G,
Dulhunty Angela F,
Casarotto Marco G
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05130.x
Subject(s) - ryanodine receptor , loop (graph theory) , ryr1 , chemistry , biophysics , receptor , mutant , cooperativity , stereochemistry , biochemistry , biology , crystallography , gene , mathematics , combinatorics
SUMMARY1 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. 2 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. 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 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. 5 The mutant E1108A located in the negatively charged loop of SPRY2 reduces the binding affinity to the DHPR II–III loop.