Structure based computational assessment of channel properties of assembled ORF-8a from SARS-CoV.
ORF 8a is a short 39 amino acid bitopic membrane protein encoded by severe acute respiratory syndrome causing corona virus (SARS-CoV). It has been identified to increase permeability of the lipid membrane for cations. Permeability is suggested to occur due to the assembly of helical bundles. Computational models of a pentameric assembly of 8a peptides are generated using the first 22 amino acids, which include the transmembrane domain. Low energy structures reveal a hydrophilic pore mantled by residues Thr-8, and -18, Ser-11, Cys-13, and Arg-22. Potential of mean force (PMF) profiles for mono (Na(+) , K(+) , Cl(-) ) and divalent (Ca(2+) ) ions along the pore are calculated. The data support experimental findings of a weak cation selectivity of the channel. Calculations on 8a are compared to data derived for a pentameric bundle consisting of the M2 helices of the bacterial pentameric ligand gated ion channel GLIC (3EHZ). PMF curves of both, bundles 8a and M2, show sigmoidal shaped profiles. In comparison to the data for the M2-GLIC model, data of the 8a bundle show lower amplitude of the PMF values between maximum and minimum and less discrimination amongst ions.
Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, 112, Taiwan; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, 112, Taiwan.
Hao-Jen
HJ
Hsu
Meng-Han
MH
Lin
Christina
C
Schindler
Wolfgang B
WB
Fischer
D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010539:Permeability; D011188:Potassium / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry*
D007473:Ion Channels; D014764:Viral Proteins; D012964:Sodium; D011188:Potassium
ORF 8a; SARS-CoV; ion selectivity; membrane protein; molecular dynamics simulations; protein assembly; viral ion channel