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• W2803177263 endingPage "10856" @default.
• W2803177263 startingPage "10843" @default.
• W2803177263 abstract "The conformational changes of a calcium transport ATPase were investigated with molecular dynamics (MD) simulations as well as fluorescence resonance energy transfer (FRET) measurements to determine the significance of a discrete structural element for regulation of the conformational dynamics of the transport cycle. Previous MD simulations indicated that a loop in the cytosolic domain of the SERCA calcium transporter facilitates an open-to-closed structural transition. To investigate the significance of this structural element, we performed additional MD simulations and new biophysical measurements of SERCA structure and function. Rationally designed in silico mutations of three acidic residues of the loop decreased SERCA domain–domain contacts and increased domain–domain separation distances. Principal component analysis of MD simulations suggested decreased sampling of compact conformations upon N-loop mutagenesis. Deficits in headpiece structural dynamics were also detected by measuring intramolecular FRET of a Cer–YFP–SERCA construct (2-color SERCA). Compared with WT, the mutated 2-color SERCA shows a partial FRET response to calcium, whereas retaining full responsiveness to the inhibitor thapsigargin. Functional measurements showed that the mutated transporter still hydrolyzes ATP and transports calcium, but that maximal enzyme activity is reduced while maintaining similar calcium affinity. In live cells, calcium elevations resulted in concomitant FRET changes as the population of WT 2-color SERCA molecules redistributed among intermediates of the transport cycle. Our results provide novel insights on how the population of SERCA pumps responds to dynamic changes in intracellular calcium. The conformational changes of a calcium transport ATPase were investigated with molecular dynamics (MD) simulations as well as fluorescence resonance energy transfer (FRET) measurements to determine the significance of a discrete structural element for regulation of the conformational dynamics of the transport cycle. Previous MD simulations indicated that a loop in the cytosolic domain of the SERCA calcium transporter facilitates an open-to-closed structural transition. To investigate the significance of this structural element, we performed additional MD simulations and new biophysical measurements of SERCA structure and function. Rationally designed in silico mutations of three acidic residues of the loop decreased SERCA domain–domain contacts and increased domain–domain separation distances. Principal component analysis of MD simulations suggested decreased sampling of compact conformations upon N-loop mutagenesis. Deficits in headpiece structural dynamics were also detected by measuring intramolecular FRET of a Cer–YFP–SERCA construct (2-color SERCA). Compared with WT, the mutated 2-color SERCA shows a partial FRET response to calcium, whereas retaining full responsiveness to the inhibitor thapsigargin. Functional measurements showed that the mutated transporter still hydrolyzes ATP and transports calcium, but that maximal enzyme activity is reduced while maintaining similar calcium affinity. In live cells, calcium elevations resulted in concomitant FRET changes as the population of WT 2-color SERCA molecules redistributed among intermediates of the transport cycle. Our results provide novel insights on how the population of SERCA pumps responds to dynamic changes in intracellular calcium." @default.
• W2803177263 created "2018-06-01" @default.
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• W2803177263 date "2018-07-01" @default.
• W2803177263 modified "2023-10-16" @default.
• W2803177263 title "Redistribution of SERCA calcium pump conformers during intracellular calcium signaling" @default.
• W2803177263 cites W100274011 @default.
• W2803177263 cites W1164720054 @default.
• W2803177263 cites W1499221564 @default.
• W2803177263 cites W1501972593 @default.
• W2803177263 cites W1558754585 @default.
• W2803177263 cites W1570016694 @default.
• W2803177263 cites W1577862498 @default.
• W2803177263 cites W1597612174 @default.
• W2803177263 cites W1743793701 @default.
• W2803177263 cites W1763024183 @default.
• W2803177263 cites W1965681212 @default.
• W2803177263 cites W1966078827 @default.
• W2803177263 cites W1966112781 @default.
• W2803177263 cites W1969230335 @default.
• W2803177263 cites W1976499671 @default.
• W2803177263 cites W1977480282 @default.
• W2803177263 cites W1979856860 @default.
• W2803177263 cites W1986324389 @default.
• W2803177263 cites W1990708284 @default.
• W2803177263 cites W1991794210 @default.
• W2803177263 cites W2000413656 @default.
• W2803177263 cites W2001687277 @default.
• W2803177263 cites W2007848144 @default.
• W2803177263 cites W2012380402 @default.
• W2803177263 cites W2013578935 @default.
• W2803177263 cites W2017245188 @default.
• W2803177263 cites W2018591170 @default.
• W2803177263 cites W2025518120 @default.
• W2803177263 cites W2029667189 @default.
• W2803177263 cites W2029854679 @default.
• W2803177263 cites W2030039514 @default.
• W2803177263 cites W2034366277 @default.
• W2803177263 cites W2035266068 @default.
• W2803177263 cites W2038583780 @default.
• W2803177263 cites W2041638382 @default.
• W2803177263 cites W2057646264 @default.
• W2803177263 cites W2067596891 @default.
• W2803177263 cites W2067678773 @default.
• W2803177263 cites W2081693079 @default.
• W2803177263 cites W2085569207 @default.
• W2803177263 cites W2085711301 @default.
• W2803177263 cites W2090055042 @default.
• W2803177263 cites W2091603217 @default.
• W2803177263 cites W2092149908 @default.
• W2803177263 cites W2094218961 @default.
• W2803177263 cites W2094517427 @default.
• W2803177263 cites W2095145098 @default.
• W2803177263 cites W2098505754 @default.
• W2803177263 cites W2098550162 @default.
• W2803177263 cites W2099783463 @default.
• W2803177263 cites W2103522217 @default.
• W2803177263 cites W2106754238 @default.
• W2803177263 cites W2109503333 @default.
• W2803177263 cites W2112929918 @default.
• W2803177263 cites W2114663994 @default.
• W2803177263 cites W2114846189 @default.
• W2803177263 cites W2125602632 @default.
• W2803177263 cites W2132589721 @default.
• W2803177263 cites W2134336691 @default.
• W2803177263 cites W2145537234 @default.
• W2803177263 cites W2145559031 @default.
• W2803177263 cites W2153331570 @default.
• W2803177263 cites W2154720198 @default.
• W2803177263 cites W2158714558 @default.
• W2803177263 cites W2160544821 @default.
• W2803177263 cites W2162145234 @default.
• W2803177263 cites W2162855904 @default.
• W2803177263 cites W2167279371 @default.
• W2803177263 cites W2171392062 @default.
• W2803177263 cites W2180912470 @default.
• W2803177263 cites W2213754585 @default.
• W2803177263 cites W2216376837 @default.
• W2803177263 cites W2271175958 @default.
• W2803177263 cites W2327229155 @default.
• W2803177263 cites W2395427107 @default.
• W2803177263 cites W2408454168 @default.
• W2803177263 cites W2522133100 @default.
• W2803177263 cites W2548318386 @default.
• W2803177263 cites W2613629789 @default.
• W2803177263 cites W2767990740 @default.
• W2803177263 cites W2777903947 @default.
• W2803177263 cites W2809198214 @default.
• W2803177263 doi "https://doi.org/10.1074/jbc.ra118.002472" @default.
• W2803177263 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6052202" @default.
• W2803177263 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29764938" @default.
• W2803177263 hasPublicationYear "2018" @default.

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