Dystrophin needs your vote!



Cartoon representation - colored by secondary structures



Many may quickly overlook dystrophin as just another ordinary protein; its importance no greater than the rest. The protein’s structure doesn’t jump off the page like some of the others, there is nothing special or complex about the name, and we’ve never mentioned it in Biochem so of course it can have no significance right? Wrong. Dystrophin actually acts as a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. The importance of its bodily function becomes apparent when the protein is lacking. Dystrophin deficiency has been definitively established as one of the root causes of muscular dystrophy; mainly Duchenne muscular dystrophy (DMD). In patients with DMD, the absence of dystrophin leads to the loss of all dystrophin-associated proteins, causing the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. This may render the sarcolemma vulnerable to physical stress. DMD is a severe x-linked recessive form of muscular dystrophy characterized by the rapid progression of muscular degeneration, eventually leading to loss of ambulation and death. It affects 1 in every 4,000 males making it the most prevalent form of muscular dystrophy. It starts with muscle weakness and loss of muscle mass by the age of five starting in the legs and pelvis while working its way up to the arms and neck. Usually by age ten patients are in braces and by twelve confined to a wheelchair. The continual decline eventually leads to paralysis. Life expectancy is in the late teens to early twenties. 

Surface representation - colored by chains
Kinda looks like some sort of monster

Dystrophin's structure is an antiparallel dimer each comprising two calponin homology domains that are linked by a central alpha helix. Its N-terminal domain binds to F-actin and its C terminus binds to the dystrophin-associated glycoprotein (DAG) complex in the membrane. It 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.

References:

Norwood, F. L., A. J. Sutherland-Smith, N. H. Keep, and J. Kendrick-Jones. "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." Structure 8.481 (2000). Web. 17 Mar. 2011.

Tinsley, J. M., D. J. Blake, M Pearce, A. E. Knight, and J. Kendrick-Jones. "Dystrophin and related proteins." Current Opinion in Genetic Developement 3.3 June (1993): 484-90. Web. 17 Mar. 2011.

Matsumura, K, and KP Campbell. "Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophies." Muscle Verve 17.1 Jan. (1994): 2-15. Web. 17 Mar. 2011.

Dystrophin - Most Interesting Protein on Earth

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.

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. It 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. Mutations within dystrophin can result in Duchenne or Becker muscular dystrophy. Duchenne muscular dystrophy (DMD) is a severe recessive X-linked form of muscular dystrophy characterized by rapid progression of muscle degeneration, eventually leading to loss of ambulation and death.Becker muscular dystrophy (also known as Benign pseudohypertrophic muscular dystrophy) is an X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis. The structure is an antiparallel dimer of two ABDs each comprising two calponin homology domains that are linked by a central alpha helix.

Norwood, F. L., A. J. Sutherland-Smith, N. H. Keep, and J. Kendrick-Jones. "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." Structure 8.481 (2000). Web. 17 Mar. 2011.

Dystrophin and related proteins.

During the past year significant progress has been made in understanding how dystrophin deficiency leads to muscle cell necrosis in Duchenne muscular dystrophy and Becker muscular dystrophy. Dystrophin interacts with a glycoprotein complex spanning the muscle sarcolemma, effectively linking the actin cytoskeleton to the extracellular matrix. The carboxyl terminus of dystrophin is required for glycoprotein binding. Interestingly, at least three mRNAs transcribed from the distal end of the DMD gene in tissues other than muscle have been shown to encode this domain. Deficiency of a second component of the dystrophin-associated glycoprotein complex has been shown to occur in another muscle-wasting disorder, severe childhood autosomal recessive muscular dystrophy. Sequence analysis of the entire cDNA for the autosomal dystrophin-related protein utrophin has shown that dystrophin and utrophin are closely related. Furthermore, both of these proteins have been shown to bind to the same or a similar glycoprotein complex in muscle.

Tinsley, J. M., D. J. Blake, M Pearce, A. E. Knight, and J. Kendrick-Jones. "Dystrophin and related proteins." Current Opinion in Genetic Developement 3.3 June (1993): 484-90. Web. 17 Mar. 2011.

Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophies.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is associated with a large oligomeric complex of sarcolemmal glycoproteins, including dystroglycan which provides a linkage to the extracellular matrix component, laminin. In patients with DMD, the absence of dystrophin leads to the loss in all of the dystrophin-associated proteins, causing the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. This may render the sarcolemma vulnerable to physical stress. These recent developments in the research concerning the function of the dystrophin-glycoprotein complex pave a way for the better understanding of the pathogenesis of muscular dystrophies.

Matsumura, K, and KP Campbell. "Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophies." Muscle Verve 17.1 Jan. (1994): 2-15. Web. 17 Mar. 2011.

Dystrophin Representations

The first image is a cartoon representation with the secondary structures colored.

The second image is a stick representation on a black background

The third image I really just felt looked cool.

The fourth image is seen from a different angle with a light grey background. It is colored by chains rather than secondary structures.

The fifth image is switched back to a black background and has a sphere representation.