Prediction of tyrosine sulfation in seven-transmembrane peptide receptors.
Posttranslational modification by tyrosine sulfation regulates many important protein protein interactions and modulates the binding affinity and specificity of seventransmembrane peptide receptors. We developed a log-odds position-specific-scoring-matrix (PSSM) to accurately predict tyrosine sulfation using 62 tyrosine sites known to be sulfated and 421 tyrosine sites known not to be sulfated. We predict that 49 tyrosines of 32 seven-transmembrane peptide receptors are sulfated. Although we did not incorporate characteristics of confirmed sulfation sites such as clustering and conservation across species into our PSSM, our predicted sites nevertheless exhibited these characteristics. The observed conservation suggests that there are strong evolutionary pressures to preserve selected biological activity of seven-transmembrane receptors. The predicted tyrosine sulfation sites predominantly occur in the extracellular tail and extracellular loop 2, regions consistent with their association with binding pockets of the receptor.
Yu
Kristine M
KM
Section of Neurobiology, Physiology, and Behavior, University of California, Davis 95616, USA.
Liu
Justin
J
Moy
Ryan
R
Lin
Henry C
HC
Nicholas
Hugh B
HB
Rosenquist
Grace L
GL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D017433:Protein Structure, Secondary; D018019:Receptors, Corticotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism; D011962:Receptors, FSH / Q000737:chemistry / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D018027:Receptors, Glucagon / Q000737:chemistry / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism; D011974:Receptors, LH / Q000737:chemistry / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry* / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D014443:Tyrosine / Q000032:analysis / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018019:Receptors, Corticotropin-Releasing Hormone; D011962:Receptors, FSH; D044042:Receptors, Formyl Peptide; D018027:Receptors, Glucagon; D011971:Receptors, Immunologic; D011974:Receptors, LH; D018000:Receptors, Peptide; D013431:Sulfates; D014443:Tyrosine; D000099052:CRF Receptor, Type 1