User:Gag224/Wikipedia.org/wiki/M protein (Streptococcus)

There are over 200 known serotypes of M proteins, which is what allows an individual to become infected with more than one member of the Streptococcus family. Of the known serotypes, M1 and M3 are most commonly associated with pneumonia and deep soft tissue infections.

Structure
Under a microscope, M protein appears as a fibrous coat on the surface of the cell, looking akin to a tennis ball. The structure of the M protein is a fibrillar protein with a non-ideal α-helical coiled-coil configuration. The design of the molecule bears resemblance to other mammalian proteins, such as the rabbit skeletal muscle tropomyosin. The overall size of M protein varies, both between different serotypes and the same serotype, with variations between 41,000 and 60,000 molecular weight.

Both the N-terminus and C-terminus have two unique features. The first is the presence of imperfect repeats in the sequence. Even among closely related M protein types, the repetitions in the N-terminus are not closely related, though they do become much more closely related in the C-Terminus and D-Region. The second is that with the exception of the first 20 residues of the HVR and the C-Terminus except for the last ~50-residues of the D-region, the M protein has α-helical coiled-coil heptad periodicity.

Function
M proteins bind to many proteins, which include fibrinogen, albumin, plasminogen, immunoglobulin, Factor H and C4b binding protein. The M1 protein can also activate leukocytes, thus inciting inflammatory responses. The C-Terminus region is what allows M proteins to bind to factor H. Although other regions contribute to the M protein’s ability to resist phagocytosis, Streptococcus that do not have M proteins will struggle to survive in human blood that contains phagocytes.

In Streptococcus zooepidemicus, M proteins facilitate the invasion of the brain thanks to membrane vesicles bound to it, which is absorbed by human brain endothelial microvascular cells through endocytosis, causing a disruption to the blood-brain barrier.

Identification of Streptococcus pyogenes
Regions of the genes of M proteins can be used for the identification of Streptococcus pyogenes and the resulting Group A Streptococcal infection (GAS). By using oligonucleotide probes derived from sequences of the N-terminus region, different serotypes can be identified from one another.

Vaccines
Development of vaccines that target M proteins is widely sought after, since the M protein is capable of binding many proteins that regulate innate and acquired immune systems. At least one vaccinia virus containing the genes to produce M proteins has shown viability for animal trials.