This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2qvk
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2qvk.jpg|left|200px]] | [[Image:2qvk.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2qvk", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_2qvk| PDB=2qvk | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis''' | '''The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis''' | ||
| Line 29: | Line 26: | ||
[[Category: Cascio, D.]] | [[Category: Cascio, D.]] | ||
[[Category: Chaptal, V.]] | [[Category: Chaptal, V.]] | ||
| - | [[Category: | + | [[Category: Calcium binding domain]] |
| - | [[Category: | + | [[Category: Cbd2]] |
| - | [[Category: | + | [[Category: Metal binding protein]] |
| - | [[Category: | + | [[Category: Sodium calcium exchanger]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:45:47 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 12:45, 4 May 2008
The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis
Overview
The Na(+)-Ca(2+) exchanger plays a central role in cardiac contractility by maintaining Ca(2+) homeostasis. Two Ca(2+)-binding domains, CBD1 and CBD2, located in a large intracellular loop, regulate activity of the exchanger. Ca(2+) binding to these regulatory domains activates the transport of Ca(2+) across the plasma membrane. Previously, we solved the structure of CBD1, revealing four Ca(2+) ions arranged in a tight planar cluster. Here, we present structures of CBD2 in the Ca(2+)-bound (1.7-A resolution) and -free (1.4-A resolution) conformations. Like CBD1, CBD2 has a classical Ig fold but coordinates only two Ca(2+) ions in primary and secondary Ca(2+) sites. In the absence of Ca(2+), Lys(585) stabilizes the structure by coordinating two acidic residues (Asp(552) and Glu(648)), one from each of the Ca(2+)-binding sites, and prevents a substantial protein unfolding. We have mutated all of the acidic residues that coordinate the Ca(2+) ions and have examined the effects of these mutations on regulation of exchange activity. Three mutations (E516L, D578V, and E648L) at the primary Ca(2+) site completely remove Ca(2+) regulation, placing the exchanger into a constitutively active state. These are the first data defining the role of CBD2 as a regulatory domain in the Na(+)-Ca(2+) exchanger.
About this Structure
2QVK is a Single protein structure of sequence from Canis lupus familiaris. Full crystallographic information is available from OCA.
Reference
The second Ca2+-binding domain of the Na+ Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis., Besserer GM, Ottolia M, Nicoll DA, Chaptal V, Cascio D, Philipson KD, Abramson J, Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18467-72. Epub 2007 Oct 25. PMID:17962412 Page seeded by OCA on Sun May 4 15:45:47 2008
