Can mutational GC-pressure create new linear B-cell epitopes in herpes simplex virus type 1 glycoprotein B?
We showed that GC-content of nucleotide sequences coding for linear B-cell epitopes of herpes simplex virus type 1 (HSV1) glycoprotein B (gB) is higher than GC-content of sequences coding for epitope-free regions of this glycoprotein (G + C = 73 and 64%, respectively). Linear B-cell epitopes have been predicted in HSV1 gB by BepiPred algorithm ( www.cbs.dtu.dk/services/BepiPred ). Proline is an acrophilic amino acid residue (it is usually situated on the surface of protein globules, and so included in linear B-cell epitopes). Indeed, the level of proline is much higher in predicted epitopes of gB than in epitope-free regions (17.8% versus 1.8%). This amino acid is coded by GC-rich codons (CCX) that can be produced due to nucleotide substitutions caused by mutational GC-pressure. GC-pressure will also lead to disappearance of acrophobic phenylalanine, isoleucine, methionine and tyrosine coded by GC-poor codons. Results of our "in-silico directed mutagenesis" showed that single nonsynonymous substitutions in AT to GC direction in two long epitope-free regions of gB will cause formation of new linear epitopes or elongation of previously existing epitopes flanking these regions in 25% of 539 possible cases. The calculations of GC-content and amino acid content have been performed by CodonChanges algorithm ( www.barkovsky.hotmail.ru ).
Khrustalev
Vladislav Victorovich
VV
Department of General Chemistry, Belarussian State Medical University, Minsk, Belarus. vvkhrustalev@mail.ru
D000596:Amino Acids / Q000235:genetics / Q000276:immunology; D001482:Base Composition / Q000235:genetics*; D003062:Codon / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
D000596:Amino Acids; D003062:Codon; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus