PDBsum entry 4wz0

Ligase

PDB id: 4wz0

Contents

Protein chain

109 a.a.

Waters ×150

PDB id:

4wz0

Name:

Ligase

Title:

Crystal structure of u-box 1 of lubx / legu2 / lpp2887 from legionella pneumophila str. Paris

Structure:

E3 ubiquitin-protein ligase lubx. Chain: a. Fragment: residues 9-117. Synonym: legionella u-box protein. Engineered: yes

Source:

Legionella pneumophila (strain paris). Organism_taxid: 297246. Strain: paris. Gene: lubx, lpp2887. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: ril.

Resolution:

1.95Å R-factor: 0.238 R-free: 0.278

Authors:

P.J.Stogios,A.T.Quaile,T.Skarina,A.Stein,R.Di Leo,V.Yim,A.Savchenko, A.Joachimiak,Midwest Center For Structural Genomics (Mcsg)

Key ref:

A.T.Quaile et al. (2015). Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila. Structure, 23, 1459-1469. PubMed id: 26146184 DOI: 10.1016/j.str.2015.05.020

Date:

18-Nov-14 Release date: 14-Jan-15

Protein chain

Q5X159  (LUBX_LEGPA) -  E3 ubiquitin-protein ligase LubX from Legionella pneumophila (strain Paris)

Seq: 240 a.a.

Struc: 109 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1016/j.str.2015.05.020

Structure 23:1459-1469 (2015)

PubMed id: 26146184

Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila.

A.T.Quaile, M.L.Urbanus, P.J.Stogios, B.Nocek, T.Skarina, A.W.Ensminger, A.Savchenko.

ABSTRACT

LubX is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. Despite such unique features as the presence of two U-box motifs and its targeting of another effector SidH, the molecular basis of LubX activity remains poorly understood. Here we show that the N terminus of LubX is able to activate an extended number of ubiquitin-conjugating (E2) enzymes including UBE2W, UBEL6, and all tested members of UBE2D and UBE2E families. Crystal structures of LubX alone and in complex with UBE2D2 revealed drastic molecular diversification between the two U-box domains, with only the N-terminal U-box retaining E2 recognition features typical for its eukaryotic counterparts. Extensive mutagenesis followed by functional screening in a yeast model system captured functionally important LubX residues including Arg121, critical for interactions with SidH. Combined, these data provide a new molecular insight into the function of this unique pathogenic factor.