4WZ3

Crystal structure of the complex between LubX/LegU2/Lpp2887 U-box 1 and Homo sapiens UBE2D2

Summary for 4WZ3

• Entry DOI: 10.2210/pdb4wz3/pdb
• Related: 4WZ0 4WZ1 4WZ2
• Descriptor: Ubiquitin-conjugating enzyme E2 D2, E3 ubiquitin-protein ligase LubX (3 entities in total)
• Functional Keywords: alpha/beta protein, effector, activating enzyme, structural genomics, psi-biology, midwest center for structural genomics, mcsg, ligase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 41614.31

Authors

Stogios, P.J.,Quaile, A.T.,Skarina, T.,Nocek, B.,Di Leo, R.,Yim, V.,Savchenko, A.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2014-11-18, release date: 2015-01-07, Last modification date: 2024-11-20)

Primary citation

Quaile, A.T.,Urbanus, M.L.,Stogios, P.J.,Nocek, B.,Skarina, T.,Ensminger, A.W.,Savchenko, A.
Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila.
Structure, 23:1459-1469, 2015

PubMed 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.

PubMed: 26146184
DOI: 10.1016/j.str.2015.05.020

Experimental method

X-RAY DIFFRACTION (2.7 Å)