skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

Abstract

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

Authors:
 [1];  [1];  [2];  [2];  [1]; ORCiD logo [3]
  1. Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States
  2. National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
  3. Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); March of Dimes Foundation; Sidney Kimmel Foundation for Cancer Research
OSTI Identifier:
1182456
Alternate Identifier(s):
OSTI ID: 1228260; OSTI ID: 1430284
Grant/Contract Number:  
R01GM10414; P41GM103393; GM103310; FY14-251
Resource Type:
Journal Article: Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Name: eLife Journal Volume: 4; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Ye, Qiaozhen, Rosenberg, Scott C., Moeller, Arne, Speir, Jeffrey A., Su, Tiffany Y., and Corbett, Kevin D. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching. United States: N. p., 2015. Web. doi:10.7554/eLife.07367.
Ye, Qiaozhen, Rosenberg, Scott C., Moeller, Arne, Speir, Jeffrey A., Su, Tiffany Y., & Corbett, Kevin D. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching. United States. https://doi.org/10.7554/eLife.07367
Ye, Qiaozhen, Rosenberg, Scott C., Moeller, Arne, Speir, Jeffrey A., Su, Tiffany Y., and Corbett, Kevin D. 2015. "TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching". United States. https://doi.org/10.7554/eLife.07367.
@article{osti_1182456,
title = {TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching},
author = {Ye, Qiaozhen and Rosenberg, Scott C. and Moeller, Arne and Speir, Jeffrey A. and Su, Tiffany Y. and Corbett, Kevin D.},
abstractNote = {The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.},
doi = {10.7554/eLife.07367},
url = {https://www.osti.gov/biblio/1182456}, journal = {eLife},
issn = {2050-084X},
number = ,
volume = 4,
place = {United States},
year = {Tue Apr 28 00:00:00 EDT 2015},
month = {Tue Apr 28 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.7554/eLife.07367

Citation Metrics:
Cited by: 115 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Dynamics of Centromere and Kinetochore Proteins
journal, June 2004


Linking Crystallographic Model and Data Quality
journal, May 2012


The spindle-assembly checkpoint in space and time
journal, April 2007


p31comet promotes disassembly of the mitotic checkpoint complex in an ATP-dependent process
journal, February 2011


NADH-coupled microplate photometric assay for kinetic studies of ATP-hydrolyzing enzymes with low and high specific activities
journal, October 2003


Complete subunit architecture of the proteasome regulatory particle
journal, January 2012


Nucleotide Binding and Conformational Switching in the Hexameric Ring of a AAA+ Machine
journal, April 2013


Structure of the mitotic checkpoint complex
journal, March 2012


Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine
journal, January 2015


Conformation-specific binding of p31comet antagonizes the function of Mad2 in the spindle checkpoint
journal, July 2004


Dali server: conservation mapping in 3D
journal, May 2010


Accurate determination of local defocus and specimen tilt in electron microscopy
journal, June 2003


Regulation of p97 in the ubiquitin–proteasome system by the UBX protein-family
journal, January 2012


AAA+ Proteases: ATP-Fueled Machines of Protein Destruction
journal, July 2011


DoG Picker and TiltPicker: Software tools to facilitate particle selection in single particle electron microscopy
journal, May 2009


p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit
journal, November 2011


Collaboration gets the most out of software
journal, September 2013


The Chromosome Axis Controls Meiotic Events through a Hierarchical Assembly of HORMA Domain Proteins
journal, November 2014


Appion: An integrated, database-driven pipeline to facilitate EM image processing
journal, April 2009


A Meta-Analysis of Gene Expression Data Identifies a Molecular Signature Characteristic for Tumor-Stage Mycosis Fungoides
journal, August 2012


Automated molecular microscopy: The new Leginon system
journal, July 2005


Evolutionary Relationships and Structural Mechanisms of aaa+ Proteins
journal, June 2006


p31 comet acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment
journal, November 2011


Mouse TRIP13/PCH2 Is Required for Recombination and Normal Higher-Order Chromosome Structure during Meiosis
journal, August 2010


Processive ATP-driven Substrate Disassembly by the N -Ethylmaleimide-sensitive Factor (NSF) Molecular Machine
journal, June 2013


NSF N-Terminal Domain Crystal Structure
journal, July 1999


Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard
journal, May 2009


Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin
journal, January 1993


p31comet Blocks Mad2 Activation through Structural Mimicry
journal, November 2007


The Mad2 Conformational Dimer: Structure and Implications for the Spindle Assembly Checkpoint
journal, November 2007


Mechanistic insights into the recycling machine of the SNARE complex
journal, January 2015


The HORMA domain: a common structural denominator in mitotic checkpoints, chromosome synapsis and DNA repair
journal, August 1998


Determinants of conformational dimerization of Mad2 and its inhibition by p31comet
journal, March 2006


Image processing for electron microscopy single-particle analysis using XMIPP
journal, May 2008


The Mad2 spindle checkpoint protein has two distinct natively folded states
journal, March 2004


TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer
journal, July 2014


XDS
journal, January 2010


NIH Image to ImageJ: 25 years of image analysis
journal, June 2012


MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
journal, January 2013


Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine
journal, November 2009


Meiotic Chromosomes: Integrating Structure and Function
journal, December 1999


Yeast Pch2 promotes domainal axis organization, timely recombination progression, and arrest of defective recombinosomes during meiosis
journal, February 2008


Identification of a MAD2-binding protein, CMT2, and its role in mitosis
journal, December 2002


Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis
journal, May 2006


Identification of novel mitosis regulators through data mining with human centromere/kinetochore proteins as group queries
journal, January 2012


Pch2 Links Chromatin Silencing to Meiotic Checkpoint Control
journal, April 1999


Evolution and Function of the Mitotic Checkpoint
journal, August 2012


Thyroid Hormone Receptor Interacting Protein 13 (TRIP13) AAA-ATPase Is a Novel Mitotic Checkpoint-silencing Protein
journal, July 2014


Three αSNAP and 10 ATP Molecules Are Used in SNARE Complex Disassembly by N -ethylmaleimide-sensitive Factor (NSF)
journal, December 2014


XMIPP: a new generation of an open-source image processing package for electron microscopy
journal, November 2004


BUBR1 and Closed MAD2 (C-MAD2) Interact Directly to Assemble a Functional Mitotic Checkpoint Complex
journal, April 2011


Identification of markers of prostate cancer progression using candidate gene expression
journal, November 2011


A new 3-d Reconstruction Scheme Applied to the 50s Ribosomal Subunit of e. coli
journal, January 1986


Homeostatic Control of Mitotic Arrest
journal, December 2011


A New Generation of the IMAGIC Image Processing System
journal, January 1996


Phosphorylation Regulates the p31 Comet -Mitotic Arrest-deficient 2 (Mad2) Interaction to Promote Spindle Assembly Checkpoint (SAC) Activity
journal, March 2014


Features and development of Coot
journal, March 2010


MAD3 Encodes a Novel Component of the Spindle Checkpoint Which Interacts with Bub3p, Cdc20p, and Mad2p
journal, March 2000


Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2
journal, September 2001


Dendroscope 3: An Interactive Tool for Rooted Phylogenetic Trees and Networks
journal, September 2012


Crystal structure of the amino-terminal domain of N-ethylmaleimide-sensitive fusion protein
journal, June 1999


Crystal Structure of Human REV7 in Complex with a Human REV3 Fragment and Structural Implication of the Interaction between DNA Polymerase ζ and REV1
journal, February 2010


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010


The Meiotic Checkpoint Network: Step-by-Step through Meiotic Prophase
journal, October 2014


Depletion of p31 comet Protein Promotes Sensitivity to Antimitotic Drugs
journal, April 2012


Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31comet
journal, August 2014


Protein structure prediction on the Web: a case study using the Phyre server
journal, February 2009


Experimental phasing with SHELXC / D / E : combining chain tracing with density modification
journal, March 2010


ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids
journal, May 2010


Pch2 is a hexameric ring ATPase that remodels the chromosome axis protein Hop1
journal, December 2013


Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover
journal, March 2015


Dissecting the N -Ethylmaleimide-sensitive Factor : REQUIRED ELEMENTS OF THE N AND D1 DOMAINS
journal, November 2009


Jalview Version 2--a multiple sequence alignment editor and analysis workbench
journal, January 2009


[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997


Phaser crystallographic software
journal, July 2007


Closed MAD2 (C-MAD2) is selectively incorporated into the mitotic checkpoint complex (MCC)
journal, November 2011


Structure and function of the AAA+ nucleotide binding pocket
journal, January 2012


Conserved arginine residues implicated in ATP hydrolysis, nucleotide-sensing, and inter-subunit interactions in AAA and AAA+ ATPases
journal, April 2004