Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state

Liu, Wu; Schoonen, Martien; Wang, Tong; McSweeney, Sean; Liu, Qun

doi:10.1038/s42003-022-03213-2

Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state

Journal Article · Wed Mar 23 00:00:00 EDT 2022 · Communications Biology

DOI:https://doi.org/10.1038/s42003-022-03213-2· OSTI ID:1856266

Liu, Wu; Schoonen, Martien; ; McSweeney, Sean;

Abstract

AAA+ proteases regulate numerous physiological and cellular processes through tightly regulated proteolytic cleavage of protein substrates driven by ATP hydrolysis. FtsH is the only known family of membrane-anchored AAA+ proteases essential for membrane protein quality control. Although a spiral staircase rotation mechanism for substrate translocation across the FtsH pore has been proposed, the detailed conformational changes among various states have not been clear due to absence of FtsH structures in these states. We report here the cryo-EM structure for Thermotoga maritima FtsH ( Tm FtsH) in a fully ADP-bound symmetric state. Comparisons of the ADP-state structure with its apo-state and a substrate-engaged yeast YME1 structure show conformational changes in the ATPase domains, rather than the protease domains. A reconstruction of the full-length Tm FtsH provides structural insights for the dynamic transmembrane and the periplasmic domains. Our structural analyses expand the understanding of conformational switches between different nucleotide states in ATP hydrolysis by FtsH.

View Journal Article

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0012704

OSTI ID:: 1856266

Alternate ID(s):: OSTI ID: 1855083

Report Number(s):: BNL-222816-2022-JAAM; 257; PII: 3213

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 5; ISSN 2399-3642

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (49)

High‐Throughput Cloning and Expression of Integral Membrane Proteins in Escherichia coli Bruni, Renato; Kloss, Brian Current Protocols in Protein Science, Vol. 74, Issue 1 https://doi.org/10.1002/0471140864.ps2906s74	journal	November 2013
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
In vivo trapping of FtsH substrates by label-free quantitative proteomics Arends, Jan; Thomanek, Nikolas; Kuhlmann, Katja PROTEOMICS, Vol. 16, Issue 24 https://doi.org/10.1002/pmic.201600316	journal	December 2016
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3330	journal	November 2017
Stairway to translocation: AAA+ motor structures reveal the mechanisms of ATP‐dependent substrate translocation Gates, Stephanie N.; Martin, Andreas Protein Science, Vol. 29, Issue 2 https://doi.org/10.1002/pro.3743	journal	October 2019
Current developments in Coot for macromolecular model building of Electron Cryo‐microscopy and Crystallographic Data Casañal, Ana; Lohkamp, Bernhard; Emsley, Paul Protein Science, Vol. 29, Issue 4 https://doi.org/10.1002/pro.3791	journal	March 2020
Different pathways for protein degradation by the FtsH/HflKC membrane-embedded protease complex: an implication from the interference by a mutant form of a new substrate protein, YccA 1 1Edited by J. Karn Kihara, Akio; Akiyama, Yoshinori; Ito, Koreaki Journal of Molecular Biology, Vol. 279, Issue 1 https://doi.org/10.1006/jmbi.1998.1781	journal	May 1998
The inner membrane protein LapB is required for adaptation to cold stress in an LpxC-independent manner Lee, Han Byeol; Park, Si Hyoung; Lee, Chang-Ro Journal of Microbiology, Vol. 59, Issue 7 https://doi.org/10.1007/s12275-021-1130-8	journal	May 2021
Reconstitution of Membrane Proteins in Phospholipid Bilayer Nanodiscs Ritchie, T. K.; Grinkova, Y. V.; Bayburt, T. H. Methods in Enzymology https://doi.org/10.1016/S0076-6879(09)64011-8	book	January 2009
The heat shock response of Escherichia coli Arsène, Florence; Tomoyasu, Toshifumi; Bukau, Bernd International Journal of Food Microbiology, Vol. 55, Issue 1-3 https://doi.org/10.1016/S0168-1605(00)00206-3	journal	April 2000
Hexameric Ring Structure of the ATPase Domain of the Membrane-Integrated Metalloprotease FtsH from Thermus thermophilus HB8 Niwa, Hajime; Tsuchiya, Daisuke; Makyio, Hisayoshi Structure, Vol. 10, Issue 10 https://doi.org/10.1016/S0969-2126(02)00855-9	journal	October 2002
Structure and function of the bacterial AAA protease FtsH Langklotz, Sina; Baumann, Ulrich; Narberhaus, Franz Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1823, Issue 1 https://doi.org/10.1016/j.bbamcr.2011.08.015	journal	January 2012
Protein quality control in organelles — AAA/FtsH story Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1833, Issue 2 https://doi.org/10.1016/j.bbamcr.2012.03.016	journal	February 2013
Structural insights into the oligomerization of FtsH periplasmic domain from Thermotoga maritima An, Jun Yop; Sharif, Humayun; Kang, Gil Bu Biochemical and Biophysical Research Communications, Vol. 495, Issue 1 https://doi.org/10.1016/j.bbrc.2017.11.158	journal	January 2018
Gctf: Real-time CTF determination and correction Zhang, Kai Journal of Structural Biology, Vol. 193, Issue 1 https://doi.org/10.1016/j.jsb.2015.11.003	journal	January 2016
Conformational flexibility of pore loop-1 gives insights into substrate translocation by the AAA+ protease FtsH Uthoff, Matthias; Baumann, Ulrich Journal of Structural Biology, Vol. 204, Issue 2 https://doi.org/10.1016/j.jsb.2018.08.009	journal	November 2018
Mitochondrial ATP-dependent proteases in protection against accumulation of carbonylated proteins Smakowska, Elwira; Czarna, Malgorzata; Janska, Hanna Mitochondrion, Vol. 19 https://doi.org/10.1016/j.mito.2014.03.005	journal	November 2014
Structure of the Whole Cytosolic Region of ATP-Dependent Protease FtsH Suno, Ryoji; Niwa, Hajime; Tsuchiya, Daisuke Molecular Cell, Vol. 22, Issue 5 https://doi.org/10.1016/j.molcel.2006.04.020	journal	June 2006
AAA proteases in mitochondria: diverse functions of membrane-bound proteolytic machines Tatsuta, Takashi; Langer, Thomas Research in Microbiology, Vol. 160, Issue 9 https://doi.org/10.1016/j.resmic.2009.09.005	journal	November 2009
Local resolution estimates of cryoEM reconstructions Vilas, Jl; Heymann, Jb; Tagare, Hd Current Opinion in Structural Biology, Vol. 64 https://doi.org/10.1016/j.sbi.2020.06.005	journal	October 2020
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul Nature Methods, Vol. 14, Issue 4 https://doi.org/10.1038/nmeth.4193	journal	February 2017
The molecular principles governing the activity and functional diversity of AAA+ proteins Puchades, Cristina; Sandate, Colby R.; Lander, Gabriel C. Nature Reviews Molecular Cell Biology, Vol. 21, Issue 1 https://doi.org/10.1038/s41580-019-0183-6	journal	November 2019
Highly accurate protein structure prediction with AlphaFold Jumper, John; Evans, Richard; Pritzel, Alexander Nature https://doi.org/10.1038/s41586-021-03819-2	journal	July 2021
Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction Punjani, Ali; Zhang, Haowei; Fleet, David J. Nature Methods, Vol. 17, Issue 12 https://doi.org/10.1038/s41592-020-00990-8	journal	November 2020
Structure of the Bcs1 AAA-ATPase suggests an airlock-like translocation mechanism for folded proteins Kater, Lukas; Wagener, Nikola; Berninghausen, Otto Nature Structural & Molecular Biology, Vol. 27, Issue 2 https://doi.org/10.1038/s41594-019-0364-1	journal	January 2020
Structures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein Tang, Wai Kwan; Borgnia, Mario J.; Hsu, Allen L. Nature Structural & Molecular Biology, Vol. 27, Issue 2 https://doi.org/10.1038/s41594-020-0373-0	journal	February 2020
The molecular architecture of the metalloprotease FtsH Bieniossek, C.; Schalch, T.; Bumann, M. Proceedings of the National Academy of Sciences, Vol. 103, Issue 9 https://doi.org/10.1073/pnas.0600031103	journal	February 2006
The crystal structure of apo -FtsH reveals domain movements necessary for substrate unfolding and translocation Bieniossek, Christoph; Niederhauser, Barbara; Baumann, Ulrich M. Proceedings of the National Academy of Sciences, Vol. 106, Issue 51 https://doi.org/10.1073/pnas.0910708106	journal	December 2009
Quality Control of Photosystem II Yoshioka, Miho; Nakayama, Yosuke; Yoshida, Mari Journal of Biological Chemistry, Vol. 285, Issue 53 https://doi.org/10.1074/jbc.M110.117432	journal	December 2010
Electron Cryomicroscopy Structure of a Membrane-anchored Mitochondrial AAA Protease Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi Journal of Biological Chemistry, Vol. 286, Issue 6 https://doi.org/10.1074/jbc.M110.158741	journal	February 2011
A Trapping Approach Reveals Novel Substrates and Physiological Functions of the Essential Protease FtsH in Escherichia coli Westphal, Kai; Langklotz, Sina; Thomanek, Nikolas Journal of Biological Chemistry, Vol. 287, Issue 51 https://doi.org/10.1074/jbc.M112.388470	journal	December 2012
The cytoplasmic domain of the AAA+ protease FtsH is tilted with respect to the membrane to facilitate substrate entry Carvalho, Vanessa; Prabudiansyah, Irfan; Kovacik, Lubomir Journal of Biological Chemistry, Vol. 296 https://doi.org/10.1074/jbc.RA120.014739	journal	January 2021
Recent advances in understanding the assembly and repair of photosystem II Nixon, Peter J.; Michoux, Franck; Yu, Jianfeng Annals of Botany, Vol. 106, Issue 1 https://doi.org/10.1093/aob/mcq059	journal	March 2010
New insights into the QuikChangeTM process guide the use of Phusion DNA polymerase for site-directed mutagenesis Xia, Yongzhen; Chu, Wenqiao; Qi, Qingsheng Nucleic Acids Research, Vol. 43, Issue 2 https://doi.org/10.1093/nar/gku1189	journal	November 2014
ColabFold - Making protein folding accessible to all Mirdita, Milot; Schuetze, Konstantin; Moriwaki, Yoshitaka Nature Methods https://doi.org/10.1101/2021.08.15.456425	posted_content	February 2022
A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for Chloroplast Protein Import Kikuchi, Shingo; Asakura, Yukari; Imai, Midori The Plant Cell, Vol. 30, Issue 11 https://doi.org/10.1105/tpc.18.00357	journal	October 2018
A Force-Generating Machine in the Plant’s Powerhouse: A Pulling AAA-ATPase Motor Drives Protein Translocation into Chloroplasts Herrmann, Johannes M. The Plant Cell, Vol. 30, Issue 11 https://doi.org/10.1105/tpc.18.00751	journal	October 2018
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
The structure of Aquifex aeolicus FtsH in the ADP-bound state reveals a C ₂ -symmetric hexamer Vostrukhina, Marina; Popov, Alexander; Brunstein, Elena Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 6 https://doi.org/10.1107/S1399004715005945	journal	May 2015
A self-supervised workflow for particle picking in cryo-EM McSweeney, Donal M.; McSweeney, Sean M.; Liu, Qun IUCrJ, Vol. 7, Issue 4 https://doi.org/10.1107/S2052252520007241	journal	June 2020
Effects of Antibiotics and a Proto-Oncogene Homolog on Destruction of Protein Translocator SecY van Stelten, J.; Silva, F.; Belin, D. Science, Vol. 325, Issue 5941 https://doi.org/10.1126/science.1172221	journal	August 2009
Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing Puchades, Cristina; Rampello, Anthony J.; Shin, Mia Science, Vol. 358, Issue 6363 https://doi.org/10.1126/science.aao0464	journal	November 2017
YejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of Lipopolysaccharide Guest, Randi L.; Samé Guerra, Daniel; Wissler, Maria mBio, Vol. 11, Issue 2 https://doi.org/10.1128/mBio.00598-20	journal	April 2020
AAA+ Proteases: ATP-Fueled Machines of Protein Destruction Sauer, Robert T.; Baker, Tania A. Annual Review of Biochemistry, Vol. 80, Issue 1 https://doi.org/10.1146/annurev-biochem-060408-172623	journal	July 2011
When, how and why? Regulated proteolysis by the essential FtsH protease in Escherichia coli Bittner, Lisa-Marie; Arends, Jan; Narberhaus, Franz Biological Chemistry, Vol. 398, Issue 5-6 https://doi.org/10.1515/hsz-2016-0302	journal	May 2017
Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease Began, Jakub; Cordier, Baptiste; Březinová, Jana The EMBO Journal, Vol. 39, Issue 10 https://doi.org/10.15252/embj.2019102935	journal	January 2020
AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms Zhang, Shuwen; Mao, Youdong Biomolecules, Vol. 10, Issue 4 https://doi.org/10.3390/biom10040629	journal	April 2020
Regulation of the First Committed Step in Lipopolysaccharide Biosynthesis Catalyzed by LpxC Requires the Essential Protein LapC (YejM) and HslVU Protease Biernacka, Daria; Gorzelak, Patrycja; Klein, Gracjana International Journal of Molecular Sciences, Vol. 21, Issue 23 https://doi.org/10.3390/ijms21239088	journal	November 2020
New tools for automated high-resolution cryo-EM structure determination in RELION-3 Zivanov, Jasenko; Nakane, Takanori; Forsberg, Björn O. eLife, Vol. 7 https://doi.org/10.7554/eLife.42166	journal	November 2018

Similar Records

Structural insights into the oligomerization of FtsH periplasmic domain from Thermotoga maritima

Journal Article · Sun Jan 14 23:00:00 EST 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23134444

Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858)

Journal Article · Wed Apr 27 20:00:00 EDT 2016 · Journal of Bacteriology · OSTI ID:1251237

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Chaperones
Cryoelectron microscopy

Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state

Citation Formats

References (49)

Similar Records

Related Subjects