4y07

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Crystal structure of the HECT domain of human WWP2

Structural highlights

4y07 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.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

WWP2_HUMAN E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation.^[1] ^[2]

Publication Abstract from PubMed

WWP2 is a HECT-domain ubiquitin ligase of the Nedd4 family, which is involved in various important biological processes, such as protein degradation, membrane-protein sorting and transportation, the immune response, pluripotency of embryonic stem cells, tumourigenesis and metastasis. The HECT domain provides the intrinsic ubiquitin ligase activity of WWP2. Here, the expression, purification, crystallization and crystallographic analysis of the HECT domain of human WWP2 (HECT(WWP2)) are reported. HECT(WWP2) has been crystallized and the crystals diffracted to 2.50 A resolution. They belonged to space group P41212 and the structure has been solved via molecular replacement. The overall structure of HECT(WWP2) has an inverted T-shape. This structure displays a high degree of conservation with previously published structures of Nedd4 subfamily members.

Structure of the HECT domain of human WWP2.,Gong W, Zhang X, Zhang W, Li J, Li Z Acta Crystallogr F Struct Biol Commun. 2015 Oct;71(Pt 10):1251-7. doi:, 10.1107/S2053230X1501554X. Epub 2015 Sep 23. PMID:26457515^[3]

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

References

↑ Xu H, Wang W, Li C, Yu H, Yang A, Wang B, Jin Y. WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res. 2009 May;19(5):561-73. doi: 10.1038/cr.2009.31. PMID:19274063 doi:http://dx.doi.org/10.1038/cr.2009.31
↑ Chen A, Gao B, Zhang J, McEwen T, Ye SQ, Zhang D, Fang D. The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination. Mol Cell Biol. 2009 Oct;29(19):5348-56. doi: 10.1128/MCB.00407-09. Epub 2009 Aug , 3. PMID:19651900 doi:http://dx.doi.org/10.1128/MCB.00407-09
↑ Gong W, Zhang X, Zhang W, Li J, Li Z. Structure of the HECT domain of human WWP2. Acta Crystallogr F Struct Biol Commun. 2015 Oct;71(Pt 10):1251-7. doi:, 10.1107/S2053230X1501554X. Epub 2015 Sep 23. PMID:26457515 doi:http://dx.doi.org/10.1107/S2053230X1501554X