MODEL OF A PUTATIVE PORE: THE PENTAMERIC -HELICAL BUNDLE OF SARS CORONAVIRUS E PROTEIN IN LIPID BILAYERS

¹ Nanyang Technological University
² IMCB

^* To whom correspondence should be addressed. E-mail: jtorres{at}ntu.edu.sg.

Submitted on February 4, 2006
Revised on March 28, 2006
Accepted on 18 April 2006

	Abstract

The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host apoptosis and virus morphogenesis. To perform these functions, it has been suggested that protein E can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a TM pore. Indeed, in a recent study we reported that the -helical putative transmembrane domain of E protein (ETM) forms several SDS-resistant TM interactions: a dimer, a trimer and two pentameric forms. Further, these interactions were found to be evolutionarily conserved. Herein, we have studied multiple isotopically labeled ETM peptides reconstituted in model lipid bilayers, using the orientational parameters derived from infrared dichroic data. We show that the topology of ETM is consistent with a regular TM -helix. Further, the orientational parameters obtained unequivocally correspond to a homopentameric model, by comparison with previous predictions. We have independently confirmed that the full polypeptide of E protein can also aggregate as pentamers after expression in E. coli. This interaction must be stabilized, at least partially, at the TM domain. The model we report for this pentameric -helical bundle may explain some of the permabilizing properties of protein E, and should be the basis of mutagenesis efforts in future functional studies.

Key Words: coronavirus, cyano-phenylalanine, hairpin, infrared dichroism, pore, transmembrane