Hostname: page-component-7479d7b7d-t6hkb Total loading time: 0 Render date: 2024-07-11T01:28:53.067Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Beroukhim, R., and Unwin, N. (1997) Ultramicroscopy in pressGoogle Scholar

2. Taylor, K. A., Dux, L., and Martonosi, A. (1986) J. Mol. Biol. 187,417–427CrossRefGoogle Scholar

3. Castellani, L., Hardwicke, P. M, and Vibert, P. (1985) J. Mol. Biol. 185(3), 579–594CrossRefGoogle Scholar

4. Toyoshima, C, Sasabe, H., and Stokes, D. L. (1993) Nature 362,469–471CrossRefGoogle Scholar