Related Experiment Video

Updated: Jul 12, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
11:27

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

Published on: May 13, 2020

Phosphoarginine modulates oligomerization and repressor activity of mycobacterial ClpC2

Henry R Anderson1, Pratistha Kandel2, Emmanuel C Ogbonna2,3

  • 1Department of Chemistry & Biochemistry, University of Delaware, Newark, DE 19716.

Biorxiv : the Preprint Server for Biology
|July 10, 2026
PubMed

Insights

Phosphoarginine (pArg) modifies ClpC2, a transcriptional repressor, affecting its DNA binding and gene regulation. This discovery links pArg levels to bacterial gene expression, offering new insights into Mycobacterium tuberculosis.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Microbiology

Background:

  • Phosphoarginine (pArg) modifications target proteins for degradation by ClpC1P1P2, a key protease in Mycobacterium tuberculosis.
  • The regulatory roles of pArg modifications are not well understood.
  • ClpC2 is a non-proteolytic repressor homologous to ClpC1, suggesting a potential link to pArg regulation.

Purpose of the Study:

  • To investigate the mechanistic connection between pArg binding and ClpC2 activity.
  • To understand how pArg influences transcriptional regulation in mycobacteria.
  • To explore ClpC2 as a potential drug target or regulator.

Main Methods:

  • Biophysical studies to analyze ClpC2 oligomerization and DNA binding.
  • High-resolution crystal structure determination of the ClpC2 C-terminal domain.
  • In vitro assays to assess the effect of pArg and antibiotics on ClpC2 activity.
  • Comparative analysis of clpC2 promoter sequences.

Main Results:

  • ClpC2 forms higher-order oligomers that bind cooperatively to the clpC2 promoter.
  • pArg binding sterically disrupts the ClpC2 dimerization interface.
  • pArg and certain antibiotics dissociate ClpC2 from DNA, relieving transcriptional repression.
  • Differences in clpC2 promoter operator sites predict varied regulatory sensitivity across species.

Conclusions:

  • ClpC2 functions as a pArg-responsive sensor.
  • pArg levels can be mechanistically linked to downstream transcriptional regulation.
  • This study provides novel insights into the regulatory landscape of pArg modifications in mycobacteria.
Keywords:
antibioticsmycobacteriaphosphoargininestress responsetranscriptiontuberculosis

More Related Videos

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

DNA-affinity-purified Chip (DAP-chip) Method to Determine Gene Targets for Bacterial Two component Regulatory Systems12:24

DNA-affinity-purified Chip (DAP-chip) Method to Determine Gene Targets for Bacterial Two component Regulatory Systems

Published on: July 21, 2014

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...