2JRJ

Solution structure of the human Pirh2 RING-H2 domain. Northeast Structural Genomics Consortium Target HT2B

Summary for 2JRJ

• Entry DOI: 10.2210/pdb2jrj/pdb
• Descriptor: Ring finger and CHY zinc finger domain containing protein 1, ZINC ION (2 entities in total)
• Functional Keywords: ubiquitin e3 ligase, ring domain, structural genomics, protein structure initiative, psi-2, northeast structural genomics consortium, nesg, ligase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 6134.80

Authors

Sheng, Y.,Lemak, A.,Laister, R.C.,Wu, B.,Arrowsmith, C.H.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2007-06-27, release date: 2007-07-10, Last modification date: 2023-12-20)

Primary citation

Sheng, Y.,Laister, R.C.,Lemak, A.,Wu, B.,Tai, E.,Duan, S.,Lukin, J.,Sunnerhagen, M.,Srisailam, S.,Karra, M.,Benchimol, S.,Arrowsmith, C.H.
Molecular basis of Pirh2-mediated p53 ubiquitylation.
Nat.Struct.Mol.Biol., 15:1334-1342, 2008

PubMed 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.

PubMed: 19043414
DOI: 10.1038/nsmb.1521

Experimental method

SOLUTION NMR