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Structure of the Calcium Pump from Sarcoplasmic Reticulum at 8 Å Resolution: Architecture of the Transmembrane Helices and Localization of the Binding Site for Thapsigargin

Published online by Cambridge University Press:  02 July 2020

P. Zhang ,
C. Toyoshima ,
K. Yonekura ,
G. Inesi ,
M. Green  and
D.L. Stokes
P. Zhang
Affiliation:
Skirball Institute for Biomolecular Medicine, NYU Medical Center, New York, NY, 10016
C. Toyoshima
Affiliation:
Inst. for Molecular and Cellular Biosciences, Univ. of Tokyo, Tokyo, 113Japan
K. Yonekura
Affiliation:
Inst. for Molecular and Cellular Biosciences, Univ. of Tokyo, Tokyo, 113Japan
G. Inesi
Affiliation:
Dept. Biological Chemistry, Univ. of Maryland Medical School, Baltimore, MD, 21201
M. Green
Affiliation:
National Inst, for Medical Research, Mill Hill, London, NW7 1AA
D.L. Stokes
Affiliation:
Skirball Institute for Biomolecular Medicine, NYU Medical Center, New York, NY, 10016
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Extract

The calcium pump (Ca2+-ATPase) from sarcoplasmic reticulum (SR) is a prominent member of the large family of ATP-dependent cation pumps, which include Na+ /K+-ATPase, H+/K+-ATPase from the stomach, H+-ATPase from yeast and Neurospora, and various detoxifying pumps for Cd+, Cu+ and other metals. In muscle, calcium is stored inside the SR and contraction is initiated by regulated release through specific calcium channels; Ca2+ -ATPase is responsible for relaxation by pumping calcium back into the SR lumen. Many techniques (chemical modification, site mutagenesis, reaction kinetics) have been used to correlate Ca2+-ATPase sequence with function, but no high resolution three-dimensional structure of Ca2+-ATPase, or any P-type pump, has yet been determined. In the current work, we have determined the structure from helical crystals at 8 A resolution and thus revealed the alpha-helical architecture of the transmembrane domain. In addition, a specific inhibitor of Ca2+-ATPase, thapsigargin, was used to promote crystallization and we have characterized the structural consequences of its inhibition.

Type
High Resolution Protein Structures from Electron Crystallography
Information
Microscopy and Microanalysis , Volume 4 , Issue S2: Proceedings: Microscopy & Microanalysis '98, Microscopy Society of America 56th Annual Meeting, Microbeam Analysis Society 32nd Annual Meeting, Atlanta, Georgia July 12-16, 1998 , July 1998 , pp. 462 - 463
Copyright
Copyright © Microscopy Society of America

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References

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