4rxj

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crystal structure of WHSC1L1-PWWP2

Structural highlights

4rxj is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:UNX
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NSD3_HUMAN Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.[1] Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98.

Function

NSD3_HUMAN Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.[2]

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[3]

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

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Citations
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The SPARC complex defines RNAPII promoters in <i>Trypanosoma brucei</i>.
Staneva et al. (2022)
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See Also

References

  1. ↑ Tonon G, Wong KK, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, Depinho RA. High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9625-30. Epub 2005 Jun 27. PMID:15983384 doi:10.1073/pnas.0504126102
  2. ↑ Kim SM, Kee HJ, Eom GH, Choe NW, Kim JY, Kim YS, Kim SK, Kook H, Kook H, Seo SB. Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity. Biochem Biophys Res Commun. 2006 Jun 23;345(1):318-23. Epub 2006 Apr 27. PMID:16682010 doi:S0006-291X(06)00939-9
  3. ↑ 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

Contents


PDB ID 4rxj

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OCA

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