The nonideal coiled coil of M protein and its multifarious functions in pathogenesis

Partho Ghosh1

  • 1Department of Chemistry and Biochemistry, University of California, San Diego, CA, 92093-0375, USA. pghosh@ucsd.edu

Insights

Streptococcus pyogenes M protein, a key virulence factor, uses structural irregularities to interact with host components, causing disease and potentially autoimmune issues. Understanding these interactions is crucial for combating GAS infections.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Immunology

Background:

  • Streptococcus pyogenes (group A Streptococcus, GAS) is a pathogen causing mild to severe infections.
  • M protein is a major GAS virulence factor, mediating diverse interactions with host components.
  • M protein's functions include immune evasion, microcolony formation, and inducing inflammation.

Purpose of the Study:

  • To investigate the structural basis of M protein's interactions with host factors like C4BP and fibrinogen.
  • To understand how M protein's sequence nonideality contributes to GAS virulence and disease severity.
  • To explore potential links between M protein structure and autoimmune sequelae.

Main Methods:

  • Analysis of M protein's α-helical coiled coil sequence and structure.
  • Investigating interactions with host proteins, particularly C4BP and fibrinogen.
  • Comparing M protein structural features to other proteins like myosin and tropomyosin.

Main Results:

  • M protein possesses a nonideal α-helical coiled coil structure crucial for its functions.
  • Sequence nonideality leads to structural irregularities essential for fibrinogen interaction and inflammation.
  • M protein's structural features resemble those targeted in autoimmune diseases post-GAS infection.

Conclusions:

  • M protein's nonideal structure is central to its role as a virulence factor in Streptococcus pyogenes.
  • Specific structural irregularities facilitate critical host interactions, contributing to disease pathogenesis.
  • M protein's structure may play a role in the development of autoimmune conditions following GAS infections.

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.
Mechanical Protein Function01:58

Mechanical Protein Function

Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...