BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis.
The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge.
School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: sharadbt215@gmail.com.
Sharad
S
Verma
Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan 304022, India. Electronic address: sukriti1610@gmail.com.
Sukriti
S
Goyal
School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: cheta231@gmail.com.
Chetna
C
Tyagi
Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan 304022, India. Electronic address: salmaangel30@gmail.com.
Salma
S
Jamal
Department of Biotechnology, TERI University, Vasant Kunj, New Delhi 110 070, India. Electronic address: aditi225@gmail.com.
Aditi
A
Singh
School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: abhinavgr@gmail.com.
Abhinav
A
Grover
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11 / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D000072756:Protein Conformation, alpha-Helical; D000072417:Protein Domains; D055550:Protein Stability; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D051028:bcl-2-Associated X Protein
Apoptosis; BAX; BIM SAHB; Molecular dynamics simulation