Related Experiment Video

Updated: Jun 14, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.6K

Complex structure and activation mechanism of arginine kinase McsB by McsA

Kai Lu1, Bingnan Luo2, Xuan Tao1

  • 1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, GBRCE for Functional Molecular Engineering, Sun Yat-Sen University, Guangzhou, China.

Nature Chemical Biology
|September 4, 2024
PubMed

Insights

The protein arginine kinase McsB, activated by McsA, labels damaged proteins in Gram-positive bacteria. Structural and biochemical studies reveal how McsA binding activates McsB for enhanced stress response.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Microbiology

Background:

  • Protein phosphorylation is a key post-translational modification regulating cellular functions.
  • In Gram-positive bacteria, McsB (protein arginine kinase) and McsA (activator) are crucial for stress response by targeting damaged proteins.
  • The precise mechanism of McsB activation by McsA has been unclear.

Purpose of the Study:

  • To elucidate the structural basis of McsB activation by McsA.
  • To understand the role of the McsA-McsB complex in bacterial stress response.
  • To investigate how McsA binding influences McsB's kinase activity and stability.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of the McsA-McsB complex.
  • Biochemical analyses to assess kinase activity and protein interactions.
  • Thermostability assays.

Main Results:

  • The cryo-EM structure of the tetrameric McsA-McsB complex was resolved at 3.41 Å.
  • McsA's C-terminal zinc finger interacts with McsB, positioning a key catalytic cysteine residue.
  • McsA binding enhances McsB's kinase activity, increases its thermostability, and accelerates CtsR phosphorylation.
  • Homotetrameric assembly of McsB is essential for its kinase function.

Conclusions:

  • McsA binding activates McsB through specific structural interactions, enhancing its role in bacterial stress response.
  • The McsA-McsB complex provides a mechanism for efficient labeling and turnover of damaged proteins under stress conditions.
  • This study reveals the molecular details of McsB activation, offering insights into bacterial survival strategies.

More Related Videos

MS2-Affinity Purification Coupled with RNA Sequencing in Gram-Positive Bacteria08:34

MS2-Affinity Purification Coupled with RNA Sequencing in Gram-Positive Bacteria

Published on: February 23, 2021

6.7K
X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep105011:27

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

Published on: May 13, 2020

3.9K

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K
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...
8.4K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.2K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K