9d58 | pdb_00009d58
Human Dystrophin tandem calponin homology actin-binding domain crystallized in a closed-state conformation
Structural highlights
DiseaseDMD_HUMAN Defects in DMD are the cause of Duchenne muscular dystrophy (DMD) [MIM:310200. DMD is the most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment.[1] [2] [3] [4] Defects in DMD are the cause of Becker muscular dystrophy (BMD) [MIM:300376. BMD resembles DMD in hereditary and clinical features but is later in onset and more benign.[5] Defects in DMD are a cause of cardiomyopathy dilated X-linked type 3B (CMD3B) [MIM:302045; also known as X-linked dilated cardiomyopathy (XLCM). Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[6] [7] [8] FunctionDMD_HUMAN Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission.[9] Publication Abstract from PubMedThe structure of the N-terminal actin-binding domain of human dystrophin was determined at 1.94 A resolution. Each chain in the asymmetric unit exists in a ;closed' conformation, with the first and second calponin homology (CH) domains directly interacting via a 2500.6 A(2) interface. The positioning of the individual CH domains is comparable to the domain-swapped dimer seen in previous human dystrophin and utrophin actin-binding domain 1 structures. The CH1 domain is highly similar to the actin-bound utrophin structure and structural homology suggests that the ;closed' single-chain conformation opens during actin binding to mitigate steric clashes between CH2 and actin. Human dystrophin tandem calponin homology actin-binding domain crystallized in a closed-state conformation.,Streeter O, Shi K, Vavra J, Aihara H, Ervasti JM, Evans R 3rd, Muretta JM Acta Crystallogr D Struct Biol. 2025 Mar 1;81(Pt 3):122-129. doi: , 10.1107/S2059798325001457. Epub 2025 Feb 26. PMID:40007458[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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