Identification of the membrane-active regions of the severe acute respiratory syndrome coronavirus spike membrane glycoprotein using a 16/18-mer peptide scan: implications for the viral fusion mechanism.
We have identified the membrane-active regions of the severe acute respiratory syndrome coronavirus (SARS CoV) spike glycoprotein by determining the effect on model membrane integrity of a 16/18-mer SARS CoV spike glycoprotein peptide library. By monitoring the effect of this peptide library on membrane leakage in model membranes, we have identified three regions on the SARS CoV spike glycoprotein with membrane-interacting capabilities: region 1, located immediately upstream of heptad repeat 1 (HR1) and suggested to be the fusion peptide; region 2, located between HR1 and HR2, which would be analogous to the loop domain of human immunodeficiency virus type 1; and region 3, which would correspond to the pretransmembrane region. The identification of these membrane-active regions, which are capable of modifying the biophysical properties of phospholipid membranes, supports their direct role in SARS CoV-mediated membrane fusion, as well as facilitating the future development of SARS CoV entry inhibitors.
Guillén
Jaime
J
Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, E-03202 Elche-Alicante, Spain.
Pérez-Berná
Ana J
AJ
Moreno
Miguel R
MR
Villalaín
José
J
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity*; D064370:Spike Glycoprotein, Coronavirus; D013329:Structure-Activity Relationship; D013552:Swine; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
D008562:Membrane Glycoproteins; D019151:Peptide Library; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins