Structural Analysis of the Bacterial Effector AvrA Identifies a Critical Helix Involved in Substrate Recognition

Biochemistry
Jonathan M LabriolaBhushan Nagar

Abstract

Bacterial effector proteins are essential for the infection and proliferation of pathogenic bacteria through manipulation of host immune response pathways. AvrA is a Salmonella effector that belongs to the YopJ family of acetyltransferases, which suppresses c-JUN N-terminal kinase (JNK) signaling in mammals through acetylation of mitogen-activated receptor kinase kinases 4 and 7 (MKK4/7). Interestingly, there are two paralogues of AvrA that differ by only a single internal leucine residue, which when absent (AvrAΔL140) abrogates the ability to suppress JNK signaling. Here, we present the first crystal structure of a bacterial effector from an animal pathogen, AvrAΔL140, accompanied by a thorough biophysical characterization of both AvrA variants. The structure in complex with inositol hexaphosphate and coenzyme A reveals two closely associated domains consisting of a catalytic core that resembles the CE clan peptidases and a wedge-shaped regulatory region that mediates cofactor and substrate binding. The loss of the putative function of AvrAΔL140 is due to its inability to interact with MKK4/7, which ultimately arises from an altered conformation of a critical helix adjacent to the active site that harbors L140. These results p...Continue Reading

References

Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·W D Hardt, J E Galán
Apr 3, 2001·Cellular Signalling·S B Shears
Oct 2, 2004·The Journal of Biological Chemistry·Jennifer E TroskyKim Orth
Mar 29, 2006·Journal of Translational Medicine·D L Mager
Feb 17, 2007·Current Opinion in Cell Biology·Claire R Weston, Roger J Davis
Apr 7, 2007·Trends in Biochemical Sciences·Sohini MukherjeeKim Orth
Sep 21, 2007·The Journal of Biological Chemistry·Jennifer E TroskyKim Orth
Jan 23, 2009·Current Opinion in Microbiology·Emma J McGhieVassilis Koronakis
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Aug 25, 2010·Biochemical and Biophysical Research Communications·Takashi MatsumotoToshiji Tada
Nov 30, 2010·Cell·David Ribet, Pascale Cossart
Feb 10, 2012·PLoS Pathogens·Amy Huei-Yi LeeDarrell Desveaux
Feb 16, 2013·Nature Reviews. Immunology·Lynda M StuartLaurent Boyer
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·András MicsonaiJózsef Kardos
May 1, 2016·Diagnostic Microbiology and Infectious Disease·Geehan SuleymanRobert J Tibbetts
Aug 16, 2016·Nature Structural & Molecular Biology·Zhi-Min ZhangJikui Song
Oct 28, 2016·Microbiology and Molecular Biology Reviews : MMBR·Ka-Wai Ma, Wenbo Ma
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Feb 23, 2017·Molecular and Cellular Endocrinology·Rong LuJun Sun
Jul 25, 2017·Nature Plants·Zhi-Min ZhangJikui Song

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