|3lue, resolution 15.00Å ()|
|Gene:||ACTB (Homo sapiens), ACTN3 (Homo sapiens)|
Model of alpha-actinin CH1 bound to F-actin
Many actin-binding proteins contain calponin homology (CH) domains, but the manner in which these domains interact with F-actin has been controversial. Crystal structures have shown the tandem CH domains of alpha-actinin to be in a compact, closed conformation, but the interpretations of complexes of such tandem CH domains with F-actin have been ambiguous. We show that the tandem CH domains of alpha-actinin bind F-actin in an open conformation, explaining mutations that cause human diseases and suggesting that the opening of these domains may be one of the main regulatory mechanisms for proteins with tandem CH domains.
Opening of tandem calponin homology domains regulates their affinity for F-actin., Galkin VE, Orlova A, Salmazo A, Djinovic-Carugo K, Egelman EH, Nat Struct Mol Biol. 2010 May;17(5):614-6. Epub 2010 Apr 11. PMID:20383143
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[ACTB_HUMAN] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:607371]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss. Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:243310]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.
[ACTB_HUMAN] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [ACTN3_HUMAN] F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
About this Structure
- Galkin VE, Orlova A, Salmazo A, Djinovic-Carugo K, Egelman EH. Opening of tandem calponin homology domains regulates their affinity for F-actin. Nat Struct Mol Biol. 2010 May;17(5):614-6. Epub 2010 Apr 11. PMID:20383143 doi:10.1038/nsmb.1789
- ↑ Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am J Hum Genet. 2006 Jun;78(6):947-60. Epub 2006 Apr 21. PMID:16685646 doi:S0002-9297(07)63917-2
- ↑ Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4, S1-2. doi: 10.1038/ng.1091. PMID:22366783 doi:10.1038/ng.1091