Structural highlights
Function
SOPA_SALTY Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Required for inducing polymorphonuclear leukocytes migration across the intestinal epithelium. Preferentially uses host UBE2D1 (UBCH5A), UBE2D2 (UBCH5B) and UBE2L3 (UBCH7) as E2 ubiquitin-conjugating enzymes.[1] [2]
Publication Abstract from PubMed
The hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRIM65. Here we elucidate an inhibitory mechanism of TRIM56 and TRIM65 targeting by SopA. We present the crystal structure of SopA in complex with the RING domain of human TRIM56, revealing the atomic details of their interaction and the basis for SopA selectivity towards TRIM56 and TRIM65. Structure-guided biochemical analysis shows that SopA inhibits TRIM56 E3 ligase activity by occluding the E2-interacting surface of TRIM56. We further demonstrate that SopA ubiquitinates TRIM56 and TRIM65, resulting in their proteasomal degradation during infection. Our results provide the basis for how a bacterial HECT ligase blocks host RING ligases and exemplifies the multivalent power of bacterial effectors during infection.
Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA.,Fiskin E, Bhogaraju S, Herhaus L, Kalayil S, Hahn M, Dikic I Nat Commun. 2017 Jan 13;8:14004. doi: 10.1038/ncomms14004. PMID:28084320[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Y, Higashide WM, McCormick BA, Chen J, Zhou D. The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase. Mol Microbiol. 2006 Nov;62(3):786-93. PMID:17076670 doi:10.1111/j.1365-2958.2006.05407.x
- ↑ Diao J, Zhang Y, Huibregtse JM, Zhou D, Chen J. Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase. Nat Struct Mol Biol. 2008 Jan;15(1):65-70. Epub 2007 Dec 9. PMID:18066077 doi:10.1038/nsmb1346
- ↑ Fiskin E, Bhogaraju S, Herhaus L, Kalayil S, Hahn M, Dikic I. Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA. Nat Commun. 2017 Jan 13;8:14004. doi: 10.1038/ncomms14004. PMID:28084320 doi:http://dx.doi.org/10.1038/ncomms14004
