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The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity.

The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Research Abstract Details 

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  • The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Abstract Text:

    a e proudfootA E Proudfoot,s fritchleyS Fritchley,f borlatF Borlat,j p shawJ P Shaw,f vilboisF Vilbois,c zwahlenC Zwahlen,a trkolaA Trkola,d marchantD Marchant,p r claphamP R Clapham,t n wellsT N Wells,

    The chemokine RANTES (regulated on activation normal T cell expressed and secreted; CCL5) binds selectively to glycosaminoglycans (GAGs) such as heparin, chondroitin sulfate, and dermatan sulfate. The primary sequence of RANTES contains two clusters of basic residues, (44)RKNR(47) and (55)KKWVR(59). The first is a BBXB motif common in heparin-binding proteins, and the second is located in the loop directly preceding the C-terminal helix. We have mutated these residues to alanine, both as point mutations as well as triple mutations of the 40s and 50s clusters. Using a binding assay to heparin beads with radiolabeled proteins, the (44)AANA(47) mutant demonstrated an 80% reduction in its capacity to bind heparin, whereas the (55)AAWVA(59) mutant retained full binding capacity. Mutation of the (44)RKNR(47) site reduced the selectivity of RANTES binding to different GAGs. The mutants were tested for their integrity by receptor binding assays on CCR1 and CCR5 as well as their ability to induce chemotaxis in vitro. In all assays the single point mutations and the triple 50s cluster mutation caused no significant difference in activity compared with the wild type sequence. However, the triple 40s mutant showed a 80-fold reduction in affinity for CCR1, despite normal binding to CCR5. It was only able to induce monocyte chemotaxis at micromolar concentrations. The triple 40s mutant was also able to inhibit HIV-1 infectivity, but consistent with its abrogated GAG binding capacity, it no longer induced enhanced infectivity at high concentrations.

    The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Publishing Authors By Initials

    ae proudfootAE Proudfoot,s fritchleyS Fritchley,f borlatF Borlat,jp shawJP Shaw,f vilboisF Vilbois,c zwahlenC Zwahlen,a trkolaA Trkola,d marchantD Marchant,pr claphamPR Clapham,tn wellsTN Wells,

    For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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    The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: The Journal of biological chemistry

    VOLUME: 276

    Page Numbers: 10620-6

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 14

    MONTH: 12

    YEAR: 2000

    The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Keywords Mesh Terms:

    KEYWORDS: Transfection

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Information

    Substance Name: Heparin

    Registry Number: 9005-49-6

    Grant and Affiliation Information for The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity.

    AFFILIATION: Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland. amanda.proudfoot@serono.com

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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