Recent structural insights into the mechanism of ClpP protease regulation by AAA+ chaperones and small molecules

Functional cooperativity between the trigger factor chaperone and the ClpXP proteolytic complex

(2021) Kamran Rizzolo et al.   Nature Communications

Reprogramming of the Caseinolytic Protease by ADEP Antibiotics: Molecular Mechanism, Cellular Consequences, Therapeutic Potential

(2021) Heike Brötz-Oesterhelt et al.   Frontiers in Molecular Biosciences

Substrates and interactors of the ClpP protease in the mitochondria

(2021) Mark F. Mabanglo et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Recent advances in Clp protease modulation to address virulence, resistance and persistence of MRSA infection

(2021) Yuan Ju et al.   DRUG DISCOVERY TODAY

Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer

(2021) Antonella Cormio et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The ubiquitous mitochondrial protein unfoldase CLPX regulates erythroid heme synthesis by control of iron utilization and heme synthesis enzyme activation and turnover

(2021) Catherine M. Rondelli et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structures of the human LONP1 protease reveal regulatory steps involved in protease activation

(2021) Mia Shin et al.   Nature Communications

An allosteric switch regulates Mycobacterium tuberculosis ClpP1P2 protease function as established by cryo-EM and methyl-TROSY NMR

(2020) Siavash Vahidi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate

(2020) Xue Fei et al.   eLife

A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery

(2020) Zev A Ripstein et al.   eLife

Functional characterisation of ClpP mutations conferring resistance to acyldepsipeptide antibiotics in Firmicutes

(2020) Imran Tarik Malik et al.   CHEMBIOCHEM

Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis

(2020) Kyle E. Lopez et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Same structure, different mechanisms?

(2020) Francis TF Tsai et al.   eLife

ClpP regulates breast cancer cell proliferation, invasion and apoptosis by modulating the Src/PI3K/Akt signaling pathway

(2020) Juan Luo et al.   PeerJ

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

(2020) Richard T. Timms et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy

(2020) Kazem Nouri et al.   Cell Death & Disease

Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates

(2020) Xue Fei et al.   eLife

A pH-Dependent Conformational Switch Controls N. meningitidis ClpP Protease Function

(2020) Zev A. Ripstein et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Cellular proteostasis decline in human senescence

(2020) Niv Sabath et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ClpAP proteolysis does not require rotation of the ClpA unfoldase relative to ClpP

(2020) Sora Kim et al.   eLife

Development of Antibiotics That Dysregulate the Neisserial ClpP Protease

(2020) Gursonika Binepal et al.   ACS Infectious Diseases

Rufomycin Targets ClpC1 Proteolysis in Mycobacterium tuberculosis and M. abscessus

(2019) Mary P. Choules et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

N-degron and C-degron pathways of protein degradation

(2019) Alexander Varshavsky   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cryo-EM Structures of the Hsp104 Protein Disaggregase Captured in the ATP Conformation

(2019) Sukyeong Lee et al.   Cell Reports

The AAA+ protease ClpXP can easily degrade a 31 and a 52-knotted protein

(2019) Elin M. Sivertsson et al.   Scientific Reports

Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality

(2019) Jo Ishizawa et al.   CANCER CELL

ClpP Protease, a Promising Antimicrobial Target

(2019) Carlos Moreno-Cinos et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

High-Resolution Structure of ClpC1-Rufomycin and Ligand Binding Studies Provide a Framework to Design and Optimize Anti-Tuberculosis Leads

(2019) Nina M. Wolf et al.   ACS Infectious Diseases

Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control

(2019) Iryna Lytvynenko et al.   CELL

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase

(2019) Alexandrea N. Rizo et al.   Nature Communications

Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors

(2019) Jan Felix et al.   Science Advances

Cryo-EM structure of the ClpXP protein degradation machinery

(2019) Christos Gatsogiannis et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Stairway to translocation: AAA+ motor structures reveal the mechanisms of ATP‐dependent substrate translocation

(2019) Stephanie N. Gates et al.   PROTEIN SCIENCE

The functional ClpXP protease of Chlamydia trachomatis requires distinct clpP genes from separate genetic loci

(2019) Stefan Pan et al.   Scientific Reports

The Role of ClpP Protease in Bacterial Pathogenesis and Human Diseases

(2018) Vaibhav Bhandari et al.   ACS Chemical Biology

Structure and Function of the 26S Proteasome

(2018) Jared A.M. Bard et al.   Annual Review of Biochemistry

In vivo and in vitro effects of a ClpP activating antibiotic against vancomycin resistant enterococci

(2018) Autumn Brown Gandt et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Reversible inhibition of the ClpP protease via an N-terminal conformational switch

(2018) Siavash Vahidi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Dynamic structural states of ClpB involved in its disaggregation function

(2018) Takayuki Uchihashi et al.   Nature Communications

Cryo-EM structures of the archaeal PAN-proteasome reveal an around-the-ring ATPase cycle

(2018) Parijat Majumder et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pathways of cellular proteostasis in aging and disease

(2017) Courtney L. Klaips et al.   JOURNAL OF CELL BIOLOGY

Conformational control of the bacterial Clp protease by natural product antibiotics

(2017) I. T. Malik et al.   NATURAL PRODUCT REPORTS

Mutation in humanCLPXelevates levels ofδ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria

(2017) Yvette Y. Yien et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines

(2017) Adrian O. Olivares et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Knots can impair protein degradation by ATP-dependent proteases

(2017) Álvaro San Martín et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Characterization of Gain-of-Function Mutant Provides New Insights into ClpP Structure

(2016) Tengfeng Ni et al.   ACS Chemical Biology

Highly Dynamic Interactions Maintain Kinetic Stability of the ClpXP Protease During the ATP-Fueled Mechanical Cycle

(2016) Alvaro J. Amor et al.   ACS Chemical Biology

Protein quality control at the mitochondrion

(2016) W. Voos et al.   Essays in Biochemistry

Structure and Functional Properties of the Active Form of the Proteolytic Complex, ClpP1P2, fromMycobacterium tuberculosis

(2016) Mi Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Development and Characterization of Potent Cyclic Acyldepsipeptide Analogues with Increased Antimicrobial Activity

(2016) Jordan D. Goodreid et al.   JOURNAL OF MEDICINAL CHEMISTRY

Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease

(2016) Kirsten Famulla et al.   MOLECULAR MICROBIOLOGY

Substrate-translocating loops regulate mechanochemical coupling and power production in AAA+ protease ClpXP

(2016) Piere Rodriguez-Aliaga et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation

(2016) Adam L Yokom et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Open and compressed conformations ofFrancisella tularensisClpP

(2016) Laura Díaz-Sáez et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

Substrate-translocating loops regulate mechanochemical coupling and power production in AAA+ protease ClpXP

(2016) Piere Rodriguez-Aliaga et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation

(2016) Adam L Yokom et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structure and Mechanism of the Caseinolytic Protease ClpP1/2 Heterocomplex fromListeria monocytogenes

(2015) Maria Dahmen et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Organization, function and substrates of the essential Clp protease system in plastids

(2015) Kenji Nishimura et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis

(2015) Julia R. Kardon et al.   CELL

Phenyl Esters Are Potent Inhibitors of Caseinolytic Protease P and Reveal a Stereogenic Switch for Deoligomerization

(2015) Mathias W. Hackl et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine

(2015) Ohad Iosefson et al.   Nature Chemical Biology

Mechanisms of ribosome rescue in bacteria

(2015) Kenneth C. Keiler   NATURE REVIEWS MICROBIOLOGY

Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines

(2015) Adrian O. Olivares et al.   NATURE REVIEWS MICROBIOLOGY

The Mycobacterium tuberculosis ClpP1P2 Protease Interacts Asymmetrically with Its ATPase Partners ClpX and ClpC1

(2015) Julia Leodolter et al.   PLoS One

AAA+ chaperones and acyldepsipeptides activate the ClpP protease via conformational control

(2015) Malte Gersch et al.   Nature Communications

Dissection of Axial-Pore Loop Function during Unfolding and Translocation by a AAA+ Proteolytic Machine

(2015) Ohad Iosefson et al.   Cell Reports

The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo

(2014) Wei Gao et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Stochastic but Highly Coordinated Protein Unfolding and Translocation by the ClpXP Proteolytic Machine

(2014) Juan Carlos Cordova et al.   CELL

Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2

(2014) Ekaterina Gavrish et al.   CHEMISTRY & BIOLOGY

Dynamics of the ClpP serine protease: A model for self-compartmentalized proteases

(2014) Kaiyin Liu et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

Mitochondrial quality control in the myocardium: Cooperation between protein degradation and mitophagy

(2014) Babette C. Hammerling et al.   JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

Restriction of the Conformational Dynamics of the Cyclic Acyldepsipeptide Antibiotics Improves Their Antibacterial Activity

(2014) Daniel W. Carney et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery

(2014) K. R. Schmitz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The ClpXP Protease Unfolds Substrates Using a Constant Rate of Pulling but Different Gears

(2013) Maya Sen et al.   CELL

Roles of adaptor proteins in regulation of bacterial proteolysis

(2013) Aurelia Battesti et al.   CURRENT OPINION IN MICROBIOLOGY

Anti-adaptors provide multiple modes for regulation of the RssB adaptor protein

(2013) A. Battesti et al.   GENES & DEVELOPMENT

Structural Basis of Mycobacterial Inhibition by Cyclomarin A

(2013) Dileep Vasudevan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Activation of ClpP Protease by ADEP Antibiotics: Insights from Hydrogen Exchange Mass Spectrometry

(2013) Modupeola A. Sowole et al.   JOURNAL OF MOLECULAR BIOLOGY

Disruption of Oligomerization and Dehydroalanine Formation as Mechanisms for ClpP Protease Inhibition

(2013) Malte Gersch et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Mycobacterium tuberculosis ClpP Proteases Are Co-transcribed but Exhibit Different Substrate Specificities

(2013) Yoann Personne et al.   PLoS One

Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad

(2013) E. Zeiler et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Distinct quaternary structures of the AAA+ Lon protease control substrate degradation

(2013) E. F. Vieux et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The active ClpP protease fromM. tuberculosisis a complex composed of a heptameric ClpP1 and a ClpP2 ring

(2012) Tatos Akopian et al.   EMBO JOURNAL

ClpP: A structurally dynamic protease regulated by AAA+ proteins

(2012) John A. Alexopoulos et al.   JOURNAL OF STRUCTURAL BIOLOGY

Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX

(2012) Bradley R. Lowth et al.   JOURNAL OF STRUCTURAL BIOLOGY

The Natural Product Cyclomarin Kills Mycobacterium Tuberculosis by Targeting the ClpC1 Subunit of the Caseinolytic Protease

(2011) Esther K. Schmitt et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

AAA+ Proteases: ATP-Fueled Machines of Protein Destruction

(2011) Robert T. Sauer et al.   Annual Review of Biochemistry

ClpXP, an ATP-powered unfolding and protein-degradation machine

(2011) Tania A. Baker et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Proteasomal AAA-ATPases: Structure and function

(2011) Shoshana Bar-Nun et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Assembly and proteolytic processing of mycobacterial ClpP1 and ClpP2

(2011) Nadia Benaroudj et al.   BMC BIOCHEMISTRY

Single-Molecule Protein Unfolding and Translocation by an ATP-Fueled Proteolytic Machine

(2011) Marie-Eve Aubin-Tam et al.   CELL

ClpX(P) Generates Mechanical Force to Unfold and Translocate Its Protein Substrates

(2011) Rodrigo A. Maillard et al.   CELL

Activators of Cylindrical Proteases as Antimicrobials: Identification and Development of Small Molecule Activators of ClpP Protease

(2011) Elisa Leung et al.   CHEMISTRY & BIOLOGY

Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ

(2011) P. Sass et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Acyldepsipeptide Antibiotics Induce the Formation of a Structured Axial Channel in ClpP: A Model for the ClpX/ClpA-Bound State of ClpP

(2010) Dominic Him Shun Li et al.   CHEMISTRY & BIOLOGY

Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism

(2010) Byung-Gil Lee et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Local and Global Mobility in the ClpA AAA+ Chaperone Detected by Cryo-Electron Microscopy: Functional Connotations

(2010) Grégory Effantin et al.   STRUCTURE

Assembly, structure, and function of the 26S proteasome

(2010) Lynn Bedford et al.   TRENDS IN CELL BIOLOGY

Biological and Chemical Approaches to Diseases of Proteostasis Deficiency

(2009) Evan T. Powers et al.   Annual Review of Biochemistry

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

(2009) Steven E. Glynn et al.   CELL

Polypeptide Translocation by the AAA+ ClpXP Protease Machine

(2009) Sarah R. Barkow et al.   CHEMISTRY & BIOLOGY

Controlled destruction: AAA+ ATPases in protein degradation from bacteria to eukaryotes

(2009) Frank Striebel et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled protease

(2009) Janine Kirstein et al.   EMBO Molecular Medicine

Clp chaperone–proteases: structure and function

(2009) Wolfgang Kress et al.   RESEARCH IN MICROBIOLOGY

β-Lactones as Specific Inhibitors of ClpP Attenuate the Production of Extracellular Virulence Factors ofStaphylococcus aureus

(2008) Thomas Böttcher et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Diverse Pore Loops of the AAA+ ClpX Machine Mediate Unassisted and Adaptor-Dependent Recognition of ssrA-Tagged Substrates

(2008) Andreas Martin et al.   MOLECULAR CELL

Adapting Proteostasis for Disease Intervention

(2008) William E. Balch et al.   SCIENCE