Modeling the structure of SARS 3a transmembrane protein using a minimum unfavorable contact approach.

UNLABELLED

3a is an accessory protein from SARS coronavirus that is known to play a significant role in the proliferation of the virus by forming tetrameric ion channels. Although the monomeric units are known to consist of three transmembrane (TM) domains, there are no solved structures available for the complete monomer. The present study proposes a structural model for the transmembrane region of the monomer by employing our previously tested approach, which predicts potential orientations of TM -helices by minimizing the unfavorable contact surfaces between the different TM domains. The best model structure comprising all three -helices has been subjected to MD simulations to examine its quality. The TM bundle was found to form a compact and stable structure with significant intermolecular interactions. The structural features of the proposed model of 3a account for observations from previous experimental investigations on the activity of the protein. Further analysis indicates that residues from the TM2 and TM3 domains are likely to line the pore of the ion channel, which is in good agreement with a recent experimental study. In the absence of an experimental structure for the protein, the proposed structure can serve as a useful model for inferring structure-function relationships about the protein. Graphical AbstractThe structure of the membrane protein 3a from SARS coronavirus is modeled using an approach that minimizes unfavorable contacts between transmembrane domains. A structure for a complete monomeric form of the protein thereby proposed is able to account for the behavior of the protein reported in previous experimental studies.

ELECTRONIC SUPPLEMENTARY MATERIAL

The online version of this article (doi:10.1007/s12039-015-0982-z) contains supplementary material, which is available to authorized users.