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The Calcium Pumping ATPase of the Plasma Membrane Structure-Function Relatioships

  • E. Carafoli
Conference paper
Part of the NATO ASI Series book series (volume 48)

Abstract

The plasma membrane Ca ATPase is the largest of the P-type ion pumps. Its primary structure has been elucidated in rat brain and a number of human cells. The sequence of three isoforms has been described in rat brain (Shull and Greeg, 1988) and several human isoforms have been identified and sequenced in erythrocytes, teratoma cells, and other cells (Verma et al., 1988). The human teratoma pump contains 1220 amino acids, corresponding to a Mr of 134,683. Asp 475 forms the acyl phosphate during the reaction cycle, and Lys 601 binds the ATP antagonist fluoroscein isothiocyanate, and is thus part of the ATP binding site. Ten hydrophobic domains, spanning the membrane have been tentatively identified; 4 are in the N-terminal portion of the pump, 6 in the C-terminal portion. The mid portion of the pump (about 500 residues) contains no transmembrane stretches. The calmodulin (CaM) binding domain has been identified next to the C-terminus (residues 1100–1127): it ressembles the putative CaM binding regions of other CaM-modulated enzymes in its strongly basic character and its propensity to form an amphiphilic helix. The Ca dependent protease calpain attacks the CaM binding domain, removing it in two steps. In the first step about one third of the CaM binding domain is cut away leaving behind a truncated pump which still binds CaM. In the second step the entire CaM binding domain is removed. Trypsin also attacks the CaM binding domain, gradually removing the CaM sensitivity of the pump.

Keywords

Acidic Phospholipid Human Isoforms Acyl Phosphate Predicted Secondary Structure Teratoma Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Green NM (1989) APT-driven cation pumps, alignment of sequences. Trans Biochem Soc 17: 970–972.Google Scholar
  2. Shull GE, Greeg J (1988) Molecular cloning of two isoforms of the plasma membrane Ca2+-transporting APTase from rat brain. J Biol Chem 263: 8646–8657.PubMedGoogle Scholar
  3. Verma AK, Filoteo AG, Stanford DR, Wieben ED, Penniston JT, Strehler EE, Fischer R, Heim R, Vogel G, Mathews S, Strehler-Page MA, James P, Vorherr T, Krebs J, Carafoli E (1988) Complete primary structure of a human plasma membrane Ca2+ pump. J Biol Chem 263: 14152–14159.PubMedGoogle Scholar
  4. Zvaritch E, James P, Vorherr T, Falchetto R, Modyanov N and Carafoli E (1990) Mapping of functional domains in the plasma membrane Ca2+ pump. Biochemistry, in pressGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • E. Carafoli
    • 1
  1. 1.Laboratory of BiochemistrySwiss Federal Institute of Technology (ETH)ZürichSwitzerland

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