Allovalency observed by transferred NOE: interactions of sulfated tyrosine residues in the N-terminal segment of CCR5 with the CCL5 chemokine.

Autor: Kessler N; Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel., Akabayov SR; Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel., Moseri A; Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel., Cohen LS; Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, NY, USA.; PhD Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, NY, USA., Sakhapov D; Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel., Bolton D; Department of Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Office for People with Developmental Disabilities, Staten Island, NY, USA., Fridman B; Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, NY, USA., Kay LE; Department of Molecular Genetics, The University of Toronto, Toronto, ON, Canada.; Department of Biochemistry, The University of Toronto, Toronto, ON, Canada.; Department of Chemistry, The University of Toronto, Toronto, ON, Canada.; Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON, Canada., Naider F; Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, NY, USA.; PhD Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, NY, USA., Anglister J; Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2021 Mar; Vol. 288 (5), pp. 1648-1663. Date of Electronic Publication: 2020 Sep 08.
DOI: 10.1111/febs.15503
Abstrakt: The N-terminal segment of the chemokine receptor Human CC chemokine receptor 5 (CCR5), Nt-CCR5, contains four tyrosine residues, Y3, Y10, Y14, and Y15. Sulfation of at least two of these tyrosine residues was found to be essential for high-affinity binding of CCR5 to its chemokine ligands. Here, we show that among the monosulfated Nt-CCR5(8-20) peptide surrogates (sNt-CCR5) those sulfated at Y15 and Y14 have the highest affinity for the CC chemokine ligand 5 (CCL5) chemokine in comparison with monosulfation at position Y10. Sulfation at Y3 was not investigated. A peptide sulfated at both Y14 and Y15 has the highest affinity for CCL5 by up to a factor of 3, in comparison with the other disulfated (sNt-CCR5) peptides. Chemical shift perturbation analysis and transferred nuclear Overhauser effect measurements indicate that the sulfated tyrosine residues interact with the same CCL5-binding pocket and that each of the sulfated tyrosines at positions 10, 14, and 15 can occupy individually the binding site on CCL5 in a similar manner, although with somewhat different affinity, suggesting the possibility of allovalency in sulfated Nt-CCR5 peptides. The affinity of the disulfated peptides to CCL5 could be increased by this allovalency and by stronger electrostatic interactions.
(© 2020 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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