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| | <SX load='6anu' size='340' side='right' viewer='molstar' caption='[[6anu]], [[Resolution|resolution]] 7.00Å' scene=''> | | <SX load='6anu' size='340' side='right' viewer='molstar' caption='[[6anu]], [[Resolution|resolution]] 7.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6anu]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ANU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ANU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6anu]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ANU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ANU FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACTB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SPTBN2, KIAA0302, SCA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6anu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6anu OCA], [http://pdbe.org/6anu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6anu RCSB], [http://www.ebi.ac.uk/pdbsum/6anu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6anu ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6anu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6anu OCA], [https://pdbe.org/6anu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6anu RCSB], [https://www.ebi.ac.uk/pdbsum/6anu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6anu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[http://omim.org/entry/607371 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.<ref>PMID:16685646</ref> Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[http://omim.org/entry/243310 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.<ref>PMID:22366783</ref> [[http://www.uniprot.org/uniprot/SPTN2_HUMAN SPTN2_HUMAN]] Defects in SPTBN2 are the cause of spinocerebellar ataxia type 5 (SCA5) [MIM:[http://omim.org/entry/600224 600224]]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA5 is an autosomal dominant cerebellar ataxia (ADCA). It is a slowly progressive disorder with variable age at onset, ranging between 10 and 50 years.<ref>PMID:16429157</ref> | + | [https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[https://omim.org/entry/607371 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.<ref>PMID:16685646</ref> Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[https://omim.org/entry/243310 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.<ref>PMID:22366783</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[http://www.uniprot.org/uniprot/SPTN2_HUMAN SPTN2_HUMAN]] Probably plays an important role in neuronal membrane skeleton. | + | [https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Spinocerebellar ataxia type 5 (SCA5) is a neurodegenerative disease caused by mutations in the cytoskeletal protein beta-III-spectrin. Previously, a SCA5 mutation resulting in a leucine-to-proline substitution (L253P) in the actin-binding domain (ABD) was shown to cause a 1000-fold increase in actin-binding affinity. However, the structural basis for this increase is unknown. Here, we report a 6.9 A cryo-EM structure of F-actin complexed with the L253P ABD. This structure, along with co-sedimentation and pulsed-EPR measurements, demonstrates that high-affinity binding caused by the CH2-localized mutation is due to opening of the two CH domains. This enables CH1 to bind actin aided by an unstructured N-terminal region that becomes alpha-helical upon binding. This helix is required for association with actin as truncation eliminates binding. Collectively, these results shed light on the mechanism by which beta-III-spectrin, and likely similar actin-binding proteins, interact with actin, and how this mechanism can be perturbed to cause disease.
| + | |
| - | | + | |
| - | Structural basis for high-affinity actin binding revealed by a beta-III-spectrin SCA5 missense mutation.,Avery AW, Fealey ME, Wang F, Orlova A, Thompson AR, Thomas DD, Hays TS, Egelman EH Nat Commun. 2017 Nov 7;8(1):1350. doi: 10.1038/s41467-017-01367-w. PMID:29116080<ref>PMID:29116080</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6anu" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Actin 3D structures|Actin 3D structures]] | | *[[Actin 3D structures|Actin 3D structures]] |
| - | *[[Spectrin|Spectrin]] | + | *[[Spectrin 3D structures|Spectrin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Avery, A W]] | + | [[Category: Avery AW]] |
| - | [[Category: Egelman, E H]] | + | [[Category: Egelman EH]] |
| - | [[Category: Hays, T S]] | + | [[Category: Hays TS]] |
| - | [[Category: Orlova, A]] | + | [[Category: Orlova A]] |
| - | [[Category: Wang, F]] | + | [[Category: Wang F]] |
| - | [[Category: Actin binding protein]]
| + | |
| - | [[Category: Filament]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Disease
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.[1] 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.[2]
Function
ACTB_HUMAN Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
See Also
References
- ↑ 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
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