TSG‐6 interacts with hyaluronan and aggrecan in a pH‐dependent manner via a common functional element: implications for its regulation in inflamed cartilage

FEBS Letters

Parkar, Ashfaq A¹  Bayliss, Michael T²  Kahmann, Jan D¹  Day, Anthony J¹  Howat, Sarah L.T² 

[1] Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK;Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK

关键词: TSG-6;    Aggrecan;    Hyaluronan;    pH-dependent ligand binding;    Cartilage;    Inflammation;    bA-Link_TSG6;    mono-biotinylated-Link_TSG6;    b-G1;    biotinylated G1;    bHA;    biotinylated HA;    IαI;    inter-α inhibitor;    DSequiv;    molar disaccharide equivalents;    G1;    G1 domain of aggrecan;    GAG;    glycosaminoglycan;    HA;    hyaluronan;    HEPES;    N-[2-hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid];    IL-1;    interleukin-1;    Lp;    link protein;    Link_TSG6;    the recombinant Link module from human TSG-6;    NMR;    nuclear magnetic resonance;    OA;    osteoarthritis;    RA;    rheumatoid arthritis;    SAB;    standard assay buffer;    TNF;    tumour necrosis factor;    TSG-6;    TNF-stimulated gene-6;   

DOI  :  10.1016/S0014-5793(98)00523-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cartilage matrix is stabilised by the interactions of proteins with hyaluronan (HA). We compare the pH dependences of HA binding by aggrecan, link protein and TSG-6. Aggrecan and link protein exhibit maximal binding across a wide pH range (6.0–8.0). TSG-6, a protein that is only produced during inflammation, binds maximally at about pH 6.0 but shows a dramatic loss of function with increasing pH. TSG-6 also interacts with aggrecan, with a similar pH dependence, and this can be inhibited by HA. Thus, a common binding surface on TSG-6 may be involved in HA and aggrecan binding. We propose that TSG-6 is involved in matrix dissociation and that this is regulated by pH gradients in cartilage.

【 授权许可】

Unknown