6kwx

Structural highlights

Function

PSME4_HUMAN Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks.^{[1] [2] [3] [4]}

References

1. ↑ Ustrell V, Hoffman L, Pratt G, Rechsteiner M. PA200, a nuclear proteasome activator involved in DNA repair. EMBO J. 2002 Jul 1;21(13):3516-25. doi: 10.1093/emboj/cdf333. PMID:12093752 doi:http://dx.doi.org/10.1093/emboj/cdf333
2. ↑ Blickwedehl J, Agarwal M, Seong C, Pandita RK, Melendy T, Sung P, Pandita TK, Bangia N. Role for proteasome activator PA200 and postglutamyl proteasome activity in genomic stability. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16165-70. doi:, 10.1073/pnas.0803145105. Epub 2008 Oct 9. PMID:18845680 doi:http://dx.doi.org/10.1073/pnas.0803145105
3. ↑ Blickwedehl J, Olejniczak S, Cummings R, Sarvaiya N, Mantilla A, Chanan-Khan A, Pandita TK, Schmidt M, Thompson CB, Bangia N. The proteasome activator PA200 regulates tumor cell responsiveness to glutamine and resistance to ionizing radiation. Mol Cancer Res. 2012 Jul;10(7):937-44. doi: 10.1158/1541-7786.MCR-11-0493-T. Epub, 2012 May 1. PMID:22550082 doi:http://dx.doi.org/10.1158/1541-7786.MCR-11-0493-T
4. ↑ Qian MX, Pang Y, Liu CH, Haratake K, Du BY, Ji DY, Wang GF, Zhu QQ, Song W, Yu Y, Zhang XX, Huang HT, Miao S, Chen LB, Zhang ZH, Liang YN, Liu S, Cha H, Yang D, Zhai Y, Komatsu T, Tsuruta F, Li H, Cao C, Li W, Li GH, Cheng Y, Chiba T, Wang L, Goldberg AL, Shen Y, Qiu XB. Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis. Cell. 2013 May 23;153(5):1012-24. doi: 10.1016/j.cell.2013.04.032. PMID:23706739 doi:http://dx.doi.org/10.1016/j.cell.2013.04.032