2lbm

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of the ADD domain of ATRX complexed with histone tail H3 1-15 K9me3

Structural highlights

2lbm is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 25 models
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ATRX_HUMAN Defects in ATRX are the cause of alpha-thalassemia mental retardation syndrome X-linked (ATRX) [MIM:301040. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:309580; also called Carpenter-Waziri syndrome (CWS), Juberg-Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.^[11] ^[12] ^[13] ^[14] ^[15] ^[16] Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.^[17]

Function

ATRX_HUMAN Could be a global transcriptional regulator. Modifies gene expression by affecting chromatin. May be involved in brain development and facial morphogenesis.

Publication Abstract from PubMed

Accurate read-out of chromatin modifications is essential for eukaryotic life. Mutations in the gene encoding X-linked ATRX protein cause a mental-retardation syndrome, whereas wild-type ATRX protein targets pericentric and telomeric heterochromatin for deposition of the histone variant H3.3 by means of a largely unknown mechanism. Here we show that the ADD domain of ATRX, in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3 through two rigidly oriented binding pockets, one for unmodified Lys4 and the other for di- or trimethylated Lys9. In vivo experiments show this combinatorial readout is required for ATRX localization, with recruitment enhanced by a third interaction through heterochromatin protein-1 (HP1) that also recognizes trimethylated Lys9. The cooperation of ATRX ADD domain and HP1 in chromatin recruitment results in a tripartite interaction that may span neighboring nucleosomes and illustrates how the 'histone-code' is interpreted by a combination of multivalent effector-chromatin interactions.

Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin.,Eustermann S, Yang JC, Law MJ, Amos R, Chapman LM, Jelinska C, Garrick D, Clynes D, Gibbons RJ, Rhodes D, Higgs DR, Neuhaus D Nat Struct Mol Biol. 2011 Jun 12. doi: 10.1038/nsmb.2070. PMID:21666677^[18]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ. ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Hum Mol Genet. 1996 Dec;5(12):1899-907. PMID:8968741
↑ Gibbons RJ, Picketts DJ, Villard L, Higgs DR. Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell. 1995 Mar 24;80(6):837-45. PMID:7697714
↑ Villard L, Lacombe D, Fontes M. A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia. Eur J Hum Genet. 1996;4(6):316-20. PMID:9043863
↑ Gibbons RJ, Bachoo S, Picketts DJ, Aftimos S, Asenbauer B, Bergoffen J, Berry SA, Dahl N, Fryer A, Keppler K, Kurosawa K, Levin ML, Masuno M, Neri G, Pierpont ME, Slaney SF, Higgs DR. Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain. Nat Genet. 1997 Oct;17(2):146-8. PMID:9326931 doi:10.1038/ng1097-146
↑ Fichera M, Romano C, Castiglia L, Failla P, Ruberto C, Amata S, Greco D, Cardoso C, Fontes M, Ragusa A. New mutations in XNP/ATR-X gene: a further contribution to genotype/phenotype relationship in ATR/X syndrome. Mutations in brief no. 176. Online. Hum Mutat. 1998;12(3):214. PMID:10660327
↑ Lossi AM, Millan JM, Villard L, Orellana C, Cardoso C, Prieto F, Fontes M, Martinez F. Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. Am J Hum Genet. 1999 Aug;65(2):558-62. PMID:10417298 doi:10.1086/302499
↑ Villard L, Bonino MC, Abidi F, Ragusa A, Belougne J, Lossi AM, Seaver L, Bonnefont JP, Romano C, Fichera M, Lacombe D, Hanauer A, Philip N, Schwartz C, Fontes M. Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome. J Med Genet. 1999 Mar;36(3):183-6. PMID:10204841
↑ Wada T, Kubota T, Fukushima Y, Saitoh S. Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X). Am J Med Genet. 2000 Sep 18;94(3):242-8. PMID:10995512
↑ Yntema HG, Poppelaars FA, Derksen E, Oudakker AR, van Roosmalen T, Jacobs A, Obbema H, Brunner HG, Hamel BC, van Bokhoven H. Expanding phenotype of XNP mutations: mild to moderate mental retardation. Am J Med Genet. 2002 Jul 1;110(3):243-7. PMID:12116232 doi:10.1002/ajmg.10446
↑ Badens C, Martini N, Courrier S, DesPortes V, Touraine R, Levy N, Edery P. ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern. Am J Med Genet A. 2006 Oct 15;140(20):2212-5. PMID:16955409 doi:10.1002/ajmg.a.31400
↑ Villard L, Fontes M, Ades LC, Gecz J. Identification of a mutation in the XNP/ATR-X gene in a family reported as Smith-Fineman-Myers syndrome. Am J Med Genet. 2000 Mar 6;91(1):83-5. PMID:10751095
↑ Villard L, Gecz J, Mattei JF, Fontes M, Saugier-Veber P, Munnich A, Lyonnet S. XNP mutation in a large family with Juberg-Marsidi syndrome. Nat Genet. 1996 Apr;12(4):359-60. PMID:8630485 doi:http://dx.doi.org/10.1038/ng0496-359
↑ Abidi F, Schwartz CE, Carpenter NJ, Villard L, Fontes M, Curtis M. Carpenter-Waziri syndrome results from a mutation in XNP. Am J Med Genet. 1999 Jul 30;85(3):249-51. PMID:10398237
↑ Stevenson RE, Abidi F, Schwartz CE, Lubs HA, Holmes LB. Holmes-Gang syndrome is allelic with XLMR-hypotonic face syndrome. Am J Med Genet. 2000 Oct 23;94(5):383-5. PMID:11050622
↑ Leahy RT, Philip RK, Gibbons RJ, Fisher C, Suri M, Reardon W. Asplenia in ATR-X syndrome: a second report. Am J Med Genet A. 2005 Nov 15;139(1):37-9. PMID:16222662 doi:10.1002/ajmg.a.30990
↑ Wieland I, Sabathil J, Ostendorf A, Rittinger O, Ropke A, Winnepenninckx B, Kooy F, Holinski-Feder E, Wieacker P. A missense mutation in the coiled-coil motif of the HP1-interacting domain of ATR-X in a family with X-linked mental retardation. Neurogenetics. 2005 Feb;6(1):45-7. PMID:15565397 doi:10.1007/s10048-004-0190-3
↑ Gibbons RJ, Pellagatti A, Garrick D, Wood WG, Malik N, Ayyub H, Langford C, Boultwood J, Wainscoat JS, Higgs DR. Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet. 2003 Aug;34(4):446-9. PMID:12858175 doi:10.1038/ng1213
↑ Eustermann S, Yang JC, Law MJ, Amos R, Chapman LM, Jelinska C, Garrick D, Clynes D, Gibbons RJ, Rhodes D, Higgs DR, Neuhaus D. Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. Nat Struct Mol Biol. 2011 Jun 12. doi: 10.1038/nsmb.2070. PMID:21666677 doi:10.1038/nsmb.2070

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lbm"

Categories: Homo sapiens | Large Structures | Eustermann S | Neuhaus D | Yang J

@@ Line 1: / Line 1: @@
-[[Image:2lbm.png|left|200px]]
-{{STRUCTURE_2lbm|  PDB=2lbm  |  SCENE=  }}
+==Solution structure of the ADD domain of ATRX complexed with histone tail H3 1-15 K9me3==
+<StructureSection load='2lbm' size='340' side='right'caption='[[2lbm]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2lbm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LBM FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 25 models</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2lbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lbm OCA], [https://pdbe.org/2lbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lbm RCSB], [https://www.ebi.ac.uk/pdbsum/2lbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lbm ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ATRX_HUMAN ATRX_HUMAN] Defects in ATRX are the cause of alpha-thalassemia mental retardation syndrome X-linked (ATRX) [MIM:[https://omim.org/entry/301040 301040]. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.<ref>PMID:8968741</ref> <ref>PMID:7697714</ref> <ref>PMID:9043863</ref> <ref>PMID:9326931</ref> <ref>PMID:10660327</ref> <ref>PMID:10417298</ref> <ref>PMID:10204841</ref> <ref>PMID:10995512</ref> <ref>PMID:12116232</ref> <ref>PMID:16955409</ref>   Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:[https://omim.org/entry/309580 309580]; also called Carpenter-Waziri syndrome (CWS), Juberg-Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.<ref>PMID:10751095</ref> <ref>PMID:8630485</ref> <ref>PMID:10398237</ref> <ref>PMID:11050622</ref> <ref>PMID:16222662</ref> <ref>PMID:15565397</ref>   Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:[https://omim.org/entry/300448 300448]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.<ref>PMID:12858175</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/ATRX_HUMAN ATRX_HUMAN] Could be a global transcriptional regulator. Modifies gene expression by affecting chromatin. May be involved in brain development and facial morphogenesis.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Accurate read-out of chromatin modifications is essential for eukaryotic life. Mutations in the gene encoding X-linked ATRX protein cause a mental-retardation syndrome, whereas wild-type ATRX protein targets pericentric and telomeric heterochromatin for deposition of the histone variant H3.3 by means of a largely unknown mechanism. Here we show that the ADD domain of ATRX, in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3 through two rigidly oriented binding pockets, one for unmodified Lys4 and the other for di- or trimethylated Lys9. In vivo experiments show this combinatorial readout is required for ATRX localization, with recruitment enhanced by a third interaction through heterochromatin protein-1 (HP1) that also recognizes trimethylated Lys9. The cooperation of ATRX ADD domain and HP1 in chromatin recruitment results in a tripartite interaction that may span neighboring nucleosomes and illustrates how the 'histone-code' is interpreted by a combination of multivalent effector-chromatin interactions.
-===Solution structure of the ADD domain of ATRX complexed with histone tail H3 1-15 K9me3===
+Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin.,Eustermann S, Yang JC, Law MJ, Amos R, Chapman LM, Jelinska C, Garrick D, Clynes D, Gibbons RJ, Rhodes D, Higgs DR, Neuhaus D Nat Struct Mol Biol. 2011 Jun 12. doi: 10.1038/nsmb.2070. PMID:21666677<ref>PMID:21666677</ref>
-{{ABSTRACT_PUBMED_21666677}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2lbm" style="background-color:#fffaf0;"></div>
-[[2lbm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LBM OCA].
 ==See Also==
-*[[Helicase|Helicase]]
+*[[Helicase 3D structures|Helicase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:021666677</ref><references group="xtra"/>
+__TOC__
-[[Category: DNA helicase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Eustermann, S.]]
+[[Category: Large Structures]]
-[[Category: Neuhaus, D.]]
+[[Category: Eustermann S]]
-[[Category: Yang, J.]]
+[[Category: Neuhaus D]]
-[[Category: Histone tail]]
+[[Category: Yang J]]
-[[Category: Metal binding protein-structural protein complex]]

2lbm

From Proteopedia

Current revision

Solution structure of the ADD domain of ATRX complexed with histone tail H3 1-15 K9me3

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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