Regulation of chemokine recognition by site-specific tyrosine sulfation of receptor peptides.
Sulfation of tyrosine is a common posttranslational modification of secreted proteins that influences numerous physiological and pathological processes. Studies of tyrosine sulfation have been hindered by the difficulty of introducing sulfate groups at specific positions of peptides and proteins. Here we report a general strategy for synthesis of peptides containing sulfotyrosine at one or more specific position(s). The approach provides a substantial improvement in both yield and convenience over existing methods. Using synthetic sulfopeptides derived from the chemokine receptor CCR3, we demonstrate that sulfation enhances affinity for the chemokine eotaxin by approximately 7-fold or more than 28-fold, depending on which of two adjacent tyrosine residues is sulfated. The synthetic methodology will substantially enhance efforts to understand the functional and structural consequences of protein tyrosine sulfation.
Simpson
Levi S
LS
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Zhu
John Z
JZ
Widlanski
Theodore S
TS
Stone
Martin J
MJ
D001665:Binding Sites; D054413:Chemokine CCL11 / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054397:Receptors, CCR3 / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D054413:Chemokine CCL11; D010455:Peptides; D054397:Receptors, CCR3; C005662:tyrosine O-sulfate; D014443:Tyrosine