1dxx
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1dxx.gif|left|200px]] | [[Image:1dxx.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1dxx", 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_1dxx| PDB=1dxx | SCENE= }} | |
| - | + | ||
| - | | | + | |
| - | }} | + | |
'''N-TERMINAL ACTIN-BINDING DOMAIN OF HUMAN DYSTROPHIN''' | '''N-TERMINAL ACTIN-BINDING DOMAIN OF HUMAN DYSTROPHIN''' | ||
| Line 32: | Line 29: | ||
[[Category: Norwood, F L.]] | [[Category: Norwood, F L.]] | ||
[[Category: Sutherland-Smith, A J.]] | [[Category: Sutherland-Smith, A J.]] | ||
| - | [[Category: | + | [[Category: Actin-binding]] |
| - | [[Category: | + | [[Category: Calponin homology domain]] |
| - | [[Category: | + | [[Category: Dystrophin]] |
| - | [[Category: | + | [[Category: Muscular dystrophy]] |
| - | [[Category: | + | [[Category: Utrophin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:24:52 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:24, 2 May 2008
N-TERMINAL ACTIN-BINDING DOMAIN OF HUMAN DYSTROPHIN
Contents |
Overview
BACKGROUND: Dystrophin is an essential component of skeletal muscle cells. Its N-terminal domain binds to F-actin and its C terminus binds to the dystrophin-associated glycoprotein (DAG) complex in the membrane. Dystrophin is therefore thought to serve as a link from the actin-based cytoskeleton of the muscle cell through the plasma membrane to the extracellular matrix. Pathogenic mutations in dystrophin result in Duchenne or Becker muscular dystrophy. RESULTS: The crystal structure of the dystrophin actin-binding domain (ABD) has been determined at 2.6 A resolution. The structure is an antiparallel dimer of two ABDs each comprising two calponin homology domains (CH1 and CH2) that are linked by a central alpha helix. The CH domains are both alpha-helical globular folds. Comparisons with the structures of utrophin and fimbrin ABDs reveal that the conformations of the individual CH domains are very similar to those of dystrophin but that the arrangement of the two CH domains within the ABD is altered. The dystrophin dimer reveals a change of 72 degrees in the orientation of one pair of CH1 and CH2 domains (from different monomers) relative to the other pair when compared with the utrophin dimer. The dystrophin monomer is more elongated than the fimbrin ABD. CONCLUSIONS: The dystrophin ABD structure reveals a previously uncharacterised arrangement of the CH domains within the ABD. This observation has implications for the mechanism of actin binding by dystrophin and related proteins. Examining the position of three pathogenic missense mutations within the structure suggests that they exert their effects through misfolding of the ABD, rather than through disruption of the binding to F-actin.
Disease
Known disease associated with this structure: Becker muscular dystrophy OMIM:[300377], Cardiomyopathy, dilated, 3B OMIM:[300377], Duchenne muscular dystrophy OMIM:[300377]
About this Structure
1DXX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy., Norwood FL, Sutherland-Smith AJ, Keep NH, Kendrick-Jones J, Structure. 2000 May 15;8(5):481-91. PMID:10801490 Page seeded by OCA on Fri May 2 14:24:52 2008
