Background
The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the regulated and targeted proteasome-dependent degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). Non-LEE-encoded ligase (NleL) is a member of the E3 protein ligase family and cloning of the gene from Escherichia coli was first described by Kulasekara et al. (2009). Many pathogenic bacteria can deliver virulence factors into host cells that function as E3 ligases and NleL is a bacterial ubiquitin E3 ligase involved in pedestal formation (Lin et al., 2012; Piscatelli et al., 2011). NleL has been shown to contain a cysteine residue near the C terminus of the protein that forms a transient thioester bond with Ubiquitin (Piscatelli et al., 2011). Similar to eukaryotic HECT E3s ligases, NleL functions with a subgroup of E2 enzymes that contain a conserved phenylalanine residue (Lin et al., 2010). NleL also possesses the conformational flexibility characteristic of HECT E3 ligases, however, the molecular surface of NleL bears no similarity to that of HECT E3 ligases (Daio et al., 2008; Lin et al., 2010).
References
Diao J, Zhang Y, Huibregtse JM, Zhou D, Chen J. (2008) Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. Nat Struct Mol Biol 15, 65–70.
Kulasekara BR, Jacobs M, ZhouY, Wu Z, Sims E, et al. (2009) Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence. Infect Immun 77, 3713-3721.
Lin DY, Diao J, Zhou D, Chen J. (2010) Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7. J Biol Chem 286, 441–449.
Lin DY, Diao J, Chen J. (2012) Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions. PNAS 109, 1925-30.
Piscatelli H, Kotkar SA, McBee ME, Muthupalani S, Schauer DB, Mandrell RE, Leong JM, Zhou D. (2011) The EHEC type III effector NleL is an E3 ubiquitin ligase that modulates pedestal formation. PLoS One 6, e19331.