Prediction of post translation modifications at the contact site between Anaplasma phagocytophilum and human host during autophagosome induction using a bioinformatic approach.
Autophagy is crucial for maintaining physiological homeostasis, but its role in infectious diseases is not yet adequately understood. The binding of Anaplasma translocated substrate-1 (ATS1) to the human Beclin1 (BECN1) protein is responsible for the modulation of autophagy pathway. ATS1-BECN1 is a novel type of interaction that facilitates Anaplasma phagocytophilum proliferation, leading to intracellular infection via autophagosome induction and segregation from the lysosome. Currently, there is no report of post translational modifications (PTMs) of BECN1 or cross-talk required for ATS-BECN1 complex formation. Prediction/modeling of the cross-talk between phosphorylation and other PTMs (O-β-glycosylation, sumoylation, methylation and palmitoylation) has been attempted in this study, which might be responsible for regulating function after the interaction of ATS1 with BECN1. PTMs were predicted computationally and mapped onto the interface of the docked ATS1-BECN1 complex. Results show that BECN1 phosphorylation at five residues (Thr91, Ser93, Ser96, Thr141 and Ser234), the interplay with O-β-glycosylation at three sites (Thr91, Ser93 and Ser96) with ATS1 may be crucial for attachment and, hence, infection. No other PTM site at the BECN1 interface was predicted to associate with ATS1. These findings may have significant clinical implications for understanding the etiology of Anaplasma infection and for therapeutic studies.
Microbiology & Biotechnology Research Lab, Department of Environmental Sciences, Fatima Jinnah Women University, 46000 Rawalpindi, Pakistan. Electronic address: zarrin.iiui@gmail.com.
Zarrin
Z
Basharat
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, 75270 Karachi, Pakistan.
Sarah Rizwan
SR
Qazi
Microbiology & Biotechnology Research Lab, Department of Environmental Sciences, Fatima Jinnah Women University, 46000 Rawalpindi, Pakistan.
Azra
A
Yasmin
Department of Biological Sciences, Forman Christian College (A Chartered University), 54600 Lahore, Pakistan.
Syed Aoun
SA
Ali
Department of Biological Sciences, Forman Christian College (A Chartered University), 54600 Lahore, Pakistan.
Deeba Noreen
DN
Baig
D000595:Amino Acid Sequence; D041081:Anaplasma phagocytophilum / Q000378:metabolism*; D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism*; D000071186:Beclin-1 / Q000737:chemistry / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D051381:Rats; D016415:Sequence Alignment
D000071186:Beclin-1
Anaplasma phagocytophilum; Autophagy; Molecular docking; Post translational modification; Structure modeling