5vc8

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the WHSC1 PWWP1 domain

Structural highlights

5vc8 is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NSD2_HUMAN Wolf-Hirschhorn syndrome. A chromosomal aberration involving WHSC1 is a cause of multiple myeloma tumors. Translocation t(4;14)(p16.3;q32.3) with IgH. WHSC1 is located in the Wolf-Hirschhorn syndrome (WHS) critical region. WHS results from by sub-telomeric deletions in the short arm of chromosome 4. WHSC1 is deleted in every case, however deletion of linked genes contributes to both the severity of the core characteristics and the presence of the additional syndromic problems.

Function

NSD2_HUMAN Histone methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. Isoform 2 may act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The NSD proteins, namely NSD1, NSD2 and NSD3, are lysine methyltransferases, which catalyze mono- and di-methylation of histone H3K36. They are multi-domain proteins, including two PWWP domains (PWWP1 and PWWP2) separated by some other domains. These proteins act as potent oncoproteins and are implicated in various cancers. However the biological functions of these PWWP domains are still largely unknown. To better understand the functions of these proteins' PWWP domains, we cloned, expressed and purified all the PWWP domains of these NSD proteins to characterize their interactions with methylated histone peptides and dsDNA by quantitative binding assays and crystallographic analysis. Our studies indicate that all these PWWP domains except NSD1_PWWP1 bind to trimethylated H3K36, H3K79 peptides and dsDNA weakly. Our crystal structures uncover that the NDS3_PWWP2 and NSD2_PWWP1 domains, which hold an extremely long alpha-helix and alpha-helix bundle, respectively, need a conformation adjustment to interact with nucleosome.

Histone and DNA binding ability studies of the NSD subfamily of PWWP domains.,Zhang M, Yang Y, Zhou M, Dong A, Yan X, Loppnau P, Min J, Liu Y Biochem Biophys Res Commun. 2021 Jul 13;569:199-206. doi:, 10.1016/j.bbrc.2021.07.017. PMID:34271259^[4]

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

References

↑ Garlisi CG, Uss AS, Xiao H, Tian F, Sheridan KE, Wang L, Motasim Billah M, Egan RW, Stranick KS, Umland SP. A unique mRNA initiated within a middle intron of WHSC1/MMSET encodes a DNA binding protein that suppresses human IL-5 transcription. Am J Respir Cell Mol Biol. 2001 Jan;24(1):90-98. PMID:11152655
↑ Hudlebusch HR, Theilgaard-Monch K, Lodahl M, Johnsen HE, Rasmussen T. Identification of ID-1 as a potential target gene of MMSET in multiple myeloma. Br J Haematol. 2005 Sep;130(5):700-8. PMID:16115125 doi:http://dx.doi.org/BJH5664
↑ Kim JY, Kee HJ, Choe NW, Kim SM, Eom GH, Baek HJ, Kook H, Kook H, Seo SB. Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity. Mol Cell Biol. 2008 Mar;28(6):2023-34. doi: 10.1128/MCB.02130-07. Epub 2008 Jan, 2. PMID:18172012 doi:http://dx.doi.org/10.1128/MCB.02130-07
↑ Zhang M, Yang Y, Zhou M, Dong A, Yan X, Loppnau P, Min J, Liu Y. Histone and DNA binding ability studies of the NSD subfamily of PWWP domains. Biochem Biophys Res Commun. 2021 Jul 13;569:199-206. doi:, 10.1016/j.bbrc.2021.07.017. PMID:34271259 doi:http://dx.doi.org/10.1016/j.bbrc.2021.07.017

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/5vc8"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5vc8 is ON HOLD
+==Crystal structure of the WHSC1 PWWP1 domain==
+<StructureSection load='5vc8' size='340' side='right'caption='[[5vc8]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5vc8]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VC8 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DN:UNKNOWN+2-DEOXYNUCLEOTIDE'>DN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=5vc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vc8 OCA], [https://pdbe.org/5vc8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vc8 RCSB], [https://www.ebi.ac.uk/pdbsum/5vc8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vc8 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/NSD2_HUMAN NSD2_HUMAN] Wolf-Hirschhorn syndrome. A chromosomal aberration involving WHSC1 is a cause of multiple myeloma tumors. Translocation t(4;14)(p16.3;q32.3) with IgH.  WHSC1 is located in the Wolf-Hirschhorn syndrome (WHS) critical region. WHS results from by sub-telomeric deletions in the short arm of chromosome 4. WHSC1 is deleted in every case, however deletion of linked genes contributes to both the severity of the core characteristics and the presence of the additional syndromic problems.
+== Function ==
+[https://www.uniprot.org/uniprot/NSD2_HUMAN NSD2_HUMAN] Histone methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. Isoform 2 may act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment.<ref>PMID:11152655</ref> <ref>PMID:16115125</ref> <ref>PMID:18172012</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The NSD proteins, namely NSD1, NSD2 and NSD3, are lysine methyltransferases, which catalyze mono- and di-methylation of histone H3K36. They are multi-domain proteins, including two PWWP domains (PWWP1 and PWWP2) separated by some other domains. These proteins act as potent oncoproteins and are implicated in various cancers. However the biological functions of these PWWP domains are still largely unknown. To better understand the functions of these proteins' PWWP domains, we cloned, expressed and purified all the PWWP domains of these NSD proteins to characterize their interactions with methylated histone peptides and dsDNA by quantitative binding assays and crystallographic analysis. Our studies indicate that all these PWWP domains except NSD1_PWWP1 bind to trimethylated H3K36, H3K79 peptides and dsDNA weakly. Our crystal structures uncover that the NDS3_PWWP2 and NSD2_PWWP1 domains, which hold an extremely long alpha-helix and alpha-helix bundle, respectively, need a conformation adjustment to interact with nucleosome.
-Authors: Qin, S., Tempel, W., Dong, A., Bountra, C., Weigelt, J., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)
+Histone and DNA binding ability studies of the NSD subfamily of PWWP domains.,Zhang M, Yang Y, Zhou M, Dong A, Yan X, Loppnau P, Min J, Liu Y Biochem Biophys Res Commun. 2021 Jul 13;569:199-206. doi:, 10.1016/j.bbrc.2021.07.017. PMID:34271259<ref>PMID:34271259</ref>
-Description: Crystal structure of the WHSC1 PWWP1 domain
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Arrowsmith, C.H]]
+<div class="pdbe-citations 5vc8" style="background-color:#fffaf0;"></div>
-[[Category: Dong, A]]
-[[Category: Qin, S]]
+==See Also==
-[[Category: Min, J]]
+*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
-[[Category: Edwards, A.M]]
+== References ==
-[[Category: Structural Genomics Consortium (Sgc)]]
+<references/>
-[[Category: Weigelt, J]]
+__TOC__
-[[Category: Bountra, C]]
+</StructureSection>
-[[Category: Tempel, W]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Synthetic construct]]
+[[Category: Arrowsmith CH]]
+[[Category: Bountra C]]
+[[Category: Dong A]]
+[[Category: Edwards AM]]
+[[Category: Min J]]
+[[Category: Qin S]]
+[[Category: Tempel W]]
+[[Category: Weigelt J]]

5vc8

From Proteopedia

Current revision

Crystal structure of the WHSC1 PWWP1 domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox