Comparative Analyses of the Relative Effects of Various Mutations in Major Histocompatibility Complex I—a Way to Predict Protein-Protein Interactions

Abstract

Protein-protein interactions (PPIs) play pivotal roles in most of the biological processes. PPI dysfunctions are therefore associated with disease situations. Mutations often lead to PPI dysfunctions, but there are certain other types of mutations which do not cause any appreciable abnormalities. This second type of mutations is called polymorphic mutations. So far, there are many studies that deal with the identification of PPI sites, but clear-cut analyses of the involvements of mutations in PPI dysfunctions are few and far between. We therefore made an attempt to link the appearances of mutations and PPI disruptions. We used major histocompatibility complex as our reference protein complex. We analyzed the mutations leading to the disease amyloidosis and also the other mutations that do not lead to disease conditions. We computed various biophysical parameters like relative solvent accessibility to discriminate between the two different types of mutations. Our analyses for the first time came up with a plausible explanation for the effects of different types of mutations in disease development. Our future plans are to build tools to detect the effects of mutations in disease developments by disrupting the PPIs.

Proton pump inhibitors display anti‐tumour potential in glioma

“…It is reported that the acidic environment after the metabolism of tumours is not conducive to normal cells and results in the immune escape of tumour cells 73 . PPIs can directly change the quantity of T‐cell receptors (TCR) or major histocompatibility complex (MHC) so as to improve the recognition and elimination of tumour cells by T cells 74 . Alkalizing the acidic environment of tumour cells can also improve the activity of other effector cells such as natural killer cells (NK) or natural killer T cells (NKT) 75 .…”

“… 73 PPIs can directly change the quantity of T‐cell receptors (TCR) or major histocompatibility complex (MHC) so as to improve the recognition and elimination of tumour cells by T cells. 74 Alkalizing the acidic environment of tumour cells can also improve the activity of other effector cells such as natural killer cells (NK) or natural killer T cells (NKT). 75 Under the acidic environment, tumour cells can use the nutrition provided by autophagy of normal cells to meet the needs of tumour cell growth.…”