Insights from the Molecular Modelling and Docking Analysis of AIF-NLS complex to infer Nuclear Translocation of the Protein

Abstract

Apoptosis Inducing Factor protein has a dual role depending on its localization in mitochondrion (energy production) and nucleus (induces apoptosis). Cell damage transports this protein to nucleus which otherwise favors mitochondrion. The alteration of Nuclear Localisation Signal tags could aid nuclear translocation. In this study, apoptosis inducing factor protein (AIF) was conjugated with strong NLS tags and its binding affinity with Importin was studied using in silico approaches such as molecular modeling and docking. This aims to improve the docking affinity of the AIF-Importin complex thus allowing for nuclear translocation, in order to induce caspase-independent apoptosis of the cell.

Apoptosis-Inducing Factor 2 (AIF-2) Mediates a Caspase-Independent Apoptotic Pathway in the Tropical Sea Cucumber (Holothuria leucospilota)

“…In contrast, AIF lacking MLS can spontaneously bind FAD and refold into mature AIF with a potential apoptosis-promoting function [ 4 , 8 ]. Normally, AIF performs mitochondrial functions and translocates to the nucleus only under the induction of apoptotic signals [ 33 ]. Once DNA damage occurs, the permeability of the mitochondrial outer membrane changes, and AIF is released from mitochondria [ 4 , 33 ].…”

“…Normally, AIF performs mitochondrial functions and translocates to the nucleus only under the induction of apoptotic signals [ 33 ]. Once DNA damage occurs, the permeability of the mitochondrial outer membrane changes, and AIF is released from mitochondria [ 4 , 33 ]. However, subcellular localization experiments indicated that most Hl AIF-2 was localized in both the cytoplasm and nucleus of HEK293T cells without Cd 2+ treatment ( Figure 5 ).…”