The Legionella kinase LegK7 exploits the Hippo pathway scaffold protein MOB1A for allostery and substrate phosphorylation.

Proceedings of the National Academy of Sciences of the United States of America
Pei-Chung LeeMiroslaw Cygler

Abstract

During infection, the bacterial pathogen Legionella pneumophila manipulates a variety of host cell signaling pathways, including the Hippo pathway which controls cell proliferation and differentiation in eukaryotes. Our previous studies revealed that L. pneumophila encodes the effector kinase LegK7 which phosphorylates MOB1A, a highly conserved scaffold protein of the Hippo pathway. Here, we show that MOB1A, in addition to being a substrate of LegK7, also functions as an allosteric activator of its kinase activity. A crystallographic analysis of the LegK7-MOB1A complex revealed that the N-terminal half of LegK7 is structurally similar to eukaryotic protein kinases, and that MOB1A directly binds to the LegK7 kinase domain. Substitution of interface residues critical for complex formation abrogated allosteric activation of LegK7 both in vitro and within cells and diminished MOB1A phosphorylation. Importantly, the N-terminal extension (NTE) of MOB1A not only regulated complex formation with LegK7 but also served as a docking site for downstream substrates such as the transcriptional coregulator YAP1. Deletion of the NTE from MOB1A or addition of NTE peptides as binding competitors attenuated YAP1 recruitment to and phosphorylation...Continue Reading

References

Dec 1, 1977·The New England Journal of Medicine·D W FraserP S Brachman
Dec 26, 2001·Chemical Reviews·L N Johnson, R J Lewis
Dec 10, 2002·Science·G ManningS Sudarsanam
Nov 5, 2004·The Journal of Biological Chemistry·Kevin C QianBennett Farmer
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·E Krissinel, K Henrick
May 6, 2006·Biochemical and Biophysical Research Communications·Alexander HergovichBrian A Hemmings
May 9, 2007·Nature Methods·Jasmina J AllenKevan M Shokat
Mar 11, 2008·Current Biology : CB·Maria PraskovaJoseph Avruch
Sep 27, 2008·Bioinformatics·L HolmA Schenkel
May 5, 2011·Cellular Signalling·Alexander Hergovich
Dec 15, 2011·Proteome Science·Javad SafaeiSteven Pelech
Jul 27, 2012·Cell Reports·Arnau Sebé-PedrósDuojia Pan
Nov 13, 2012·The Journal of Clinical Investigation·Miki NishioAkira Suzuki
Jan 8, 2015·Protein Science : a Publication of the Protein Society·Andrey M GrishinMiroslaw Cygler
Aug 20, 2015·ACS Medicinal Chemistry Letters·W Michael SeganishXiaoda Niu
Jan 6, 2016·Genes & Development·Zhipeng MengKun-Liang Guan
Jun 24, 2016·Scientific Reports·Sun-Yong KimToshio Hakoshima
Aug 19, 2016·Science Translational Medicine·Fuqin FanDawang Zhou
Mar 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Johannes F WeijmanPeter D Mace
Apr 5, 2017·Molecular & Cellular Proteomics : MCP·Amber L CouzensAnne-Claude Gingras
Sep 28, 2017·Nature Communications·Yavuz KulaberogluAlexander Hergovich
May 20, 2018·Journal of Molecular Biology·Andrey M GrishinMiroslaw Cygler
Sep 14, 2018·Cell Host & Microbe·Pei-Chung Lee, Matthias P Machner
Apr 4, 2019·IUBMB Life·Brenden C ParkVincent S Tagliabracci

❮ Previous
Next ❯

Citations

Dec 15, 2020·Journal of Molecular Biology·Sun Cheol ParkSung-Il Yoon
Mar 3, 2021·The FEBS Journal·Andrey GrishinMiroslaw Cygler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.