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Peer-reviewedCC BY 4.0The Febs Journal

Structural insights into tyrosine sulfation of CCR5 by human tyrosylprotein sulfotransferase‐1

  • Shinnosuke Tanaka1
  • Hirai Asano1
  • Kota Toyoda1
  • Toshiaki Nishiyori1
  • Hidetaka Kojo1
  • Kazuto Kiyomatsu2
  • Katsuhisa Kurogi2
  • Yoichi Sakakibara2
  • Etsuko Nishimoto1
  • Takamasa Teramoto1
  • Yoshimitsu Kakuta1
  1. 1Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology Kyushu University Fukuoka Japan
  2. 2Faculty of Agriculture, Department of Applied Biochemistry and Biotechnology University of Miyazaki Miyazaki Japan
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Abstract

Post‐translational sulfation of the chemokine receptor CCR5 is involved in crucial biological processes such as viral infection and chemokine signaling. This sulfation can occur at the N‐terminal tyrosine residues (Y3, Y10, Y14, and Y15) of CCR5 and is catalyzed by human tyrosylprotein sulfotransferases (hTPSTs) within the Golgi lumen. However, the detailed molecular mechanism by which these tyrosine residues are sulfated remains unresolved. To elucidate the mechanism, we determined the crystal structure of a soluble domain of hTPST1 bound to the sulfate donor product 3′‐phosphoadenosine 5′‐phosphate (PAP) and a modified 18‐residue CCR5 peptide designed to isolate the Y3‐centered binding mode, at 3.2 Å resolution, with six peptide residues ordered. This structure defines key interactions consistent with Y3 sulfation and is consistent with previous biochemical data. Based on the crystal structure and prior knowledge, we constructed peptide docking models for Y10, Y14, and Y15 sulfation, as well as full‐length hTPST1‐PAP‐CCR5 docking models. The crystal structure provides experimental insight into Y3 recognition, whereas the docking models provide testable hypotheses for how the other sulfation sites may be accommodated in the context of CCR5.

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Cite

BibTeXRIS
BibTeX
@article{tanaka2026structural,
  title = {{Structural insights into tyrosine sulfation of CCR5 by human tyrosylprotein sulfotransferase‐1}},
  author = {Shinnosuke Tanaka and Hirai Asano and Kota Toyoda and Toshiaki Nishiyori and Hidetaka Kojo and Kazuto Kiyomatsu and Katsuhisa Kurogi and Yoichi Sakakibara and Etsuko Nishimoto and Takamasa Teramoto and Yoshimitsu Kakuta},
  journal = {The Febs Journal},
  year = {2026},
  month = may,
  doi = {10.1111/febs.70597},
  url = {https://doi.org/10.1111/febs.70597},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Structural insights into tyrosine sulfation of CCR5 by human tyrosylprotein sulfotransferase‐1
AU  - Shinnosuke Tanaka
AU  - Hirai Asano
AU  - Kota Toyoda
AU  - Toshiaki Nishiyori
AU  - Hidetaka Kojo
AU  - Kazuto Kiyomatsu
AU  - Katsuhisa Kurogi
AU  - Yoichi Sakakibara
AU  - Etsuko Nishimoto
AU  - Takamasa Teramoto
AU  - Yoshimitsu Kakuta
PY  - 2026
DA  - 2026/05/22
JO  - The Febs Journal
DO  - 10.1111/febs.70597
UR  - https://doi.org/10.1111/febs.70597
AB  - Post‐translational sulfation of the chemokine receptor CCR5 is involved in crucial biological processes such as viral infection and chemokine signaling. This sulfation can occur at the N‐terminal tyrosine residues (Y3, Y10, Y14, and Y15) of CCR5 and is catalyzed by human tyrosylprotein sulfotransferases (hTPSTs) within the Golgi lumen. However, the detailed molecular mechanism by which these tyrosine residues are sulfated remains unresolved. To elucidate the mechanism, we determined the crystal structure of a soluble domain of hTPST1 bound to the sulfate donor product 3′‐phosphoadenosine 5′‐phosphate (PAP) and a modified 18‐residue CCR5 peptide designed to isolate the Y3‐centered binding mode, at 3.2 Å resolution, with six peptide residues ordered. This structure defines key interactions consistent with Y3 sulfation and is consistent with previous biochemical data. Based on the crystal structure and prior knowledge, we constructed peptide docking models for Y10, Y14, and Y15 sulfation, as well as full‐length hTPST1‐PAP‐CCR5 docking models. The crystal structure provides experimental insight into Y3 recognition, whereas the docking models provide testable hypotheses for how the other sulfation sites may be accommodated in the context of CCR5.
SN  - 1742-464X
SN  - 1742-4658
ER  -