5NKZ

Crystal structure of H. polymorpha ubiquitin conjugating enzyme Pex4p in complex with soluble domain of Pex22p

Summary for 5NKZ

• Entry DOI: 10.2210/pdb5nkz/pdb
• Related: 5NL8
• Descriptor: Ubiquitin-conjugating enzyme E2-21 kDa, Peroxin 22 (2 entities in total)
• Functional Keywords: pex4, pex22, ubiquitin conjugating enzyme, crystallization, hansenula polymorpha, peroxisome import, transferase
• Biological source: Pichia angusta (Yeast); More
• Total number of polymer chains: 4
• Total formula weight: 74595.00

Authors

Danda, N.,Lunev, S.,Ali, A.,Groves, M.R.,Williams, C. (deposition date: 2017-04-03, release date: 2018-01-24, Last modification date: 2024-01-17)

Primary citation

Groves, M.R.,Schroer, C.F.E.,Middleton, A.J.,Lunev, S.,Danda, N.,Ali, A.M.,Marrink, S.J.,Williams, C.
Structural insights into K48-linked ubiquitin chain formation by the Pex4p-Pex22p complex.
Biochem. Biophys. Res. Commun., 496:562-567, 2018

PubMed Abstract: Pex4p is a peroxisomal E2 involved in ubiquitinating the conserved cysteine residue of the cycling receptor protein Pex5p. Previously, we demonstrated that Pex4p from the yeast Saccharomyces cerevisiae binds directly to the peroxisomal membrane protein Pex22p and that this interaction is vital for receptor ubiquitination. In addition, Pex22p binding allows Pex4p to specifically produce lysine 48 linked ubiquitin chains in vitro through an unknown mechanism. This activity is likely to play a role in targeting peroxisomal proteins for proteasomal degradation. Here we present the crystal structures of Pex4p alone and in complex with Pex22p from the yeast Hansenula polymorpha. Comparison of the two structures demonstrates significant differences to the active site of Pex4p upon Pex22p binding while molecular dynamics simulations suggest that Pex22p binding facilitates active site remodelling of Pex4p through an allosteric mechanism. Taken together, our data provide insights into how Pex22p binding allows Pex4p to build K48-linked Ub chains.

PubMed: 29288668
DOI: 10.1016/j.bbrc.2017.12.150

Experimental method

X-RAY DIFFRACTION (2.85 Å)