Nat Struct Mol Biol. 2008 Dec;15(12):1334-42. doi: 10.1038/nsmb.1521. Epub 2008 Nov 30.
Molecular basis of Pirh2-mediated p53 ubiquitylation.
Sheng Y1, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH.
Abstract
Pirh2
(p53-induced RING-H2 domain protein; also known as Rchy1) is an E3
ubiquitin ligase involved in a negative-feedback loop with p53. Using
NMR spectroscopy, we show that Pirh2 is a unique cysteine-rich protein
comprising three modular domains. The protein binds nine zinc ions using
a variety of zinc coordination schemes, including a RING domain and a
left-handed beta-spiral in which three zinc ions align three consecutive
small beta-sheets in an interleaved fashion. We show that Pirh2-p53
interaction is dependent on the C-terminal zinc binding module of Pirh2,
which binds to the tetramerization domain of p53. As a result, Pirh2
preferentially ubiquitylates the tetrameric form of p53 in vitro and in
vivo, suggesting that Pirh2 regulates protein turnover of the
transcriptionally active form of p53.
- PMID:
- 19043414
- PMCID:
- PMC4075976
- DOI:
- 10.1038/nsmb.1521
- [Indexed for MEDLINE]
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