The University of Southampton
University of Southampton Institutional Repository

Ca2+-ATPase structure in the E1 and E2 conformations: mechanism, helix-helix and helix-lipid interactions. [In special issue: Membrane Protein Structure]

Ca2+-ATPase structure in the E1 and E2 conformations: mechanism, helix-helix and helix-lipid interactions. [In special issue: Membrane Protein Structure]
Ca2+-ATPase structure in the E1 and E2 conformations: mechanism, helix-helix and helix-lipid interactions. [In special issue: Membrane Protein Structure]
The determination of the crystal structure of the Ca(2+)-ATPase of sarcoplasmic reticulum (SR) in its Ca(2+)-bound [Nature 405 (2000) 647] and Ca(2+)-free forms [Nature 418 (2002) 605] gives the opportunity for an analysis of conformational changes on the Ca(2+)-ATPase and of helix-helix and helix-lipid interactions in the transmembrane (TM) region of the ATPase. The locations of the ends of the TM alpha-helices on the cytoplasmic side of the membrane are reasonably well defined by the location of Trp residues and by the location of Lys-262 that snorkels up to the surface. The locations of the lumenal ends of the helices are less clear. The position of Lys-972 on the lumenal side of helix M9 suggests that the hydrophobic thickness of the protein is only about 21 A, rather than the normal 30 A. The experimentally determined TM alpha-helices do not agree well with those predicted theoretically. Charged headgroups are required for strong interaction of lipids with the ATPase, consistent with the large number of charged residues located close to the lipid-water interface. Helix packing appears to be rather irregular. Packing of helices M8 and M10 is of the 3-4 ridges-into-grooves or knobs-into-holes types. Packing of helices M5 and M7 involves two Gly residues in M7 and one Gly residue in M5. Packing of the other helices generally involves just one or two residues on each helix at the crossing point. The irregular packing of the TM alpha-helices in the Ca(2+)-ATPase, combined with the diffuse structure of the ATPase on the lumenal side of the membrane, is suggested to lead to a relative low activation energy for changing the packing of the TM alpha-helices, with changes in TM alpha-helical packing being important in the process of transfer of Ca(2+) ions across the membrane. The inhibitor thapsigargin binds in a cleft between TM alpha-helices M3, M5 and M7. It is suggested that this and other similar clefts provide binding sites for a variety of hydrophobic molecules affecting the activity of the Ca(2+)-ATPase.
sarcoplasmic reticulum, Ca2+-ATPase, lipid–protein interaction, calcium pump, helix packing, membrane protein structure TM, transmembrane, SR, ER, endoplasmic reticulum, di(C14:1)PC, dimyristoleoylphosphatidylcholine, di(C18:1)PC, dioleoylphosphatidylcholine
0304-4165
246-266
Lee, A.G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
Lee, A.G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e

Lee, A.G. (2002) Ca2+-ATPase structure in the E1 and E2 conformations: mechanism, helix-helix and helix-lipid interactions. [In special issue: Membrane Protein Structure]. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1565 (2), 246-266. (doi:10.1016/S0005-2736(02)00573-4).

Record type: Article

Abstract

The determination of the crystal structure of the Ca(2+)-ATPase of sarcoplasmic reticulum (SR) in its Ca(2+)-bound [Nature 405 (2000) 647] and Ca(2+)-free forms [Nature 418 (2002) 605] gives the opportunity for an analysis of conformational changes on the Ca(2+)-ATPase and of helix-helix and helix-lipid interactions in the transmembrane (TM) region of the ATPase. The locations of the ends of the TM alpha-helices on the cytoplasmic side of the membrane are reasonably well defined by the location of Trp residues and by the location of Lys-262 that snorkels up to the surface. The locations of the lumenal ends of the helices are less clear. The position of Lys-972 on the lumenal side of helix M9 suggests that the hydrophobic thickness of the protein is only about 21 A, rather than the normal 30 A. The experimentally determined TM alpha-helices do not agree well with those predicted theoretically. Charged headgroups are required for strong interaction of lipids with the ATPase, consistent with the large number of charged residues located close to the lipid-water interface. Helix packing appears to be rather irregular. Packing of helices M8 and M10 is of the 3-4 ridges-into-grooves or knobs-into-holes types. Packing of helices M5 and M7 involves two Gly residues in M7 and one Gly residue in M5. Packing of the other helices generally involves just one or two residues on each helix at the crossing point. The irregular packing of the TM alpha-helices in the Ca(2+)-ATPase, combined with the diffuse structure of the ATPase on the lumenal side of the membrane, is suggested to lead to a relative low activation energy for changing the packing of the TM alpha-helices, with changes in TM alpha-helical packing being important in the process of transfer of Ca(2+) ions across the membrane. The inhibitor thapsigargin binds in a cleft between TM alpha-helices M3, M5 and M7. It is suggested that this and other similar clefts provide binding sites for a variety of hydrophobic molecules affecting the activity of the Ca(2+)-ATPase.

This record has no associated files available for download.

More information

Published date: 11 October 2002
Keywords: sarcoplasmic reticulum, Ca2+-ATPase, lipid–protein interaction, calcium pump, helix packing, membrane protein structure TM, transmembrane, SR, ER, endoplasmic reticulum, di(C14:1)PC, dimyristoleoylphosphatidylcholine, di(C18:1)PC, dioleoylphosphatidylcholine

Identifiers

Local EPrints ID: 56034
URI: http://eprints.soton.ac.uk/id/eprint/56034
ISSN: 0304-4165
PURE UUID: fa048a57-cb65-4a5f-8178-3093c924b496

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 10:59

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×