The Mechanics of Calcium Transport

The Mechanics of Calcium Transport With the recent atomic models for the sarcoplasmic reticulum Ca2+-ATPase in the Ca2+-bound state, the Ca2+-free, thapsigargin-inhibited state, and the Ca2+-free, vanadate-inhibited state, we are that much closer to understanding and animating the Ca2+-transport cycle. These „snapshots” of the Ca2+-transport cycle reveal an impressive breadth and complexity of conformational change. The cytoplasmic domains undergo rigid-body movements that couple the energy of ATP to the transport of Ca2+ across the membrane. Large-scale rearrangements in the transmembrane domain suggest that the Ca2+-binding sites may alternately cease to exist and reform during the transport cycle. Of the three cytoplasmic domains, the actuator (A) domain undergoes the largest movement, namely a 110° rotation normal to the membrane. This domain is linked to transmembrane segments M1–M3, which undergo large rearrangements in the membrane domain. Together, these movements are a main event in Ca2+ transport, yet their significance is poorly understood. Nonetheless, inhibition or modulation of Ca2+-ATPase activity appears to target these conformational changes. Thapsigargin is a high-affinity inhibitor that binds to the M3 helix near Phe256, and phospholamban is a modulator of Ca2+-ATPase activity that has been cross-linked to M2 and M4. The purpose of this review is to postulate roles for the A domain and M1–M3 in Ca2+ transport and inhibition. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

The Mechanics of Calcium Transport

Loading next page...
 
/lp/springer_journal/the-mechanics-of-calcium-transport-qCFcL2ThGK
Publisher
Springer Journals
Copyright
Copyright © 2004 by Springer-Verlag
Subject
Philosophy
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-004-0666-y
Publisher site
See Article on Publisher Site

Abstract

With the recent atomic models for the sarcoplasmic reticulum Ca2+-ATPase in the Ca2+-bound state, the Ca2+-free, thapsigargin-inhibited state, and the Ca2+-free, vanadate-inhibited state, we are that much closer to understanding and animating the Ca2+-transport cycle. These „snapshots” of the Ca2+-transport cycle reveal an impressive breadth and complexity of conformational change. The cytoplasmic domains undergo rigid-body movements that couple the energy of ATP to the transport of Ca2+ across the membrane. Large-scale rearrangements in the transmembrane domain suggest that the Ca2+-binding sites may alternately cease to exist and reform during the transport cycle. Of the three cytoplasmic domains, the actuator (A) domain undergoes the largest movement, namely a 110° rotation normal to the membrane. This domain is linked to transmembrane segments M1–M3, which undergo large rearrangements in the membrane domain. Together, these movements are a main event in Ca2+ transport, yet their significance is poorly understood. Nonetheless, inhibition or modulation of Ca2+-ATPase activity appears to target these conformational changes. Thapsigargin is a high-affinity inhibitor that binds to the M3 helix near Phe256, and phospholamban is a modulator of Ca2+-ATPase activity that has been cross-linked to M2 and M4. The purpose of this review is to postulate roles for the A domain and M1–M3 in Ca2+ transport and inhibition.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jan 1, 2004

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off