Investigating the conformational dynamics of SARS-CoV-2 NSP6 protein with emphasis on non-transmembrane 91–112 & 231–290 regions

The NSP6 protein of SARS-CoV-2 is a transmembrane protein, with some regions lying outside the membrane. Besides a brief role of NSP6 in autophagosome formation, this is not studied significantly. Also, there is no structural information available to date. Based on the prediction by TMHMM server for transmembrane prediction, it is found that the N-terminal residues (1-11), middle region residues (91–112), and C-terminal residues (231–290) lies outside the membrane. Molecular Dynamics (MD) simulations showed that NSP6 consists of helical structures. In contrast, the membrane outside lying region (91–112) showed partial helicity, which was further used as a model and obtained disordered type conformation during 1.5 μs. Additionally, a 200ns simulation study of residues 231–290 have shown significant conformational changes. As compared to helical and beta-sheet conformations in its structure model, the 200ns simulation resulted in the loss of beta-sheet structures while helical regions remained intact. Further, we have experimentally characterized the residue 91–112 by using reductionist approaches. CD spectroscopy suggests that the NSP6 (91–112) is disordered-like region in isolation, which gains helical conformation in different biological mimic environmental conditions. These studies can be helpful to study NSP6 (91–112) interactions with host proteins, where different protein conformations might play a significant role. The present study adds up more information about the NSP6 protein aspect, which could be exploited for its host protein interaction and pathogenesis.