Prediction of localization and interactions of apoptotic proteins

Abstract

During apoptosis several mitochondrial proteins are released. Some of them participate in caspaseindependent nuclear DNA degradation, especially apoptosis-inducing factor (AIF) and endonuclease G (endoG). Another interesting protein, which was expected to act similarly as AIF due to the high sequence homology with AIF is AIF-homologous mitochondrion-associated inducer of death (AMID). We studied the structure, cellular localization, and interactions of several proteins in silico and also in cells using fluorescent microscopy. We found the AMID protein to be cytoplasmic, most probably incorporated into the cytoplasmic side of the lipid membranes.Bioinformatic predictions were conducted to analyze the interactions of the studied proteins with each other and with other possible partners. We conducted molecular modeling of proteins with unknown 3D structures. These models were then refined by MolProbity server and employed in molecular docking simulations of interactions. Our results show data acquired using a combination of modern in silico methods and image analysis to understand the localization, interactions and functions of proteins AMID, AIF, endonuclease G, and other apoptosis-related proteins.

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2)

“…The role of AMID in apoptosis is also unclear. By in silico methods and image analysis, the localization of AMID was predicted to be cytoplasmic, most probably incorporated into the cytoplasmic side of the cellular membranes (52,53). It was also suggested that AMID in human leukemia Jurkat T-cells after apoptosis induction is associated with the plasma membrane by immunohistochemical study (54).…”

Mechanisms and Inhibitors of Apoptosis in Cardiovascular Diseases

“…Endo G, is a conserved nuclease, normally localized in the mitochondria [69]. Its N-terminus contains a mitochondrial localization sequence (MLS), which is cleaved upon successful transport of the Endo G precursor polypeptide across the outer mitochondrial membrane [70]. From the mitochondria, Endo G translocates in the nucleus and produces DNA degradation independent of caspases [71,72].…”

In Silico Profiling of the Potentiality of Curcumin and Conventional Drugs for CagA Oncoprotein Inactivation

“…). The global energy of each complexes was considered to be related to free binding energy and its higher negative value indicates higher free binding energy and thus higher interaction probability . Based on ensemble docking analysis, it is worth noting that the predicted pharmacological activity of curcumin against H. pylori infection targeting remarkable Cag oncoprotein is encouragingly similar to conventional drugs.…”