New carbohydrate site in mutant antithrombin (7 Ile→Asn) with decreased heparin affinity

FEBS Letters

Carrell, Robin W.²  Borg, Jeanne-Yvonne⁴  Caen, Jacques¹  Soria, Claudine⁴  George, Peter M.³  Brennan, Stephen O.³  Soria, Jeannette¹ 

[1] Unite de Recherches de Thrombose et Hemostase, Unit 150 INSERM, Hospital Lariboisiere, Paris, France;Haematology Department, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, England;Molecular Pathology Laboratory, Pathology Department, Christchurch School of Medicine, Christchurch Hospital, Christchurch, New Zealand;Laboratoire D'Hemostase, Centre Hospitalier, Universitaire Rouen, Rouen 76038 Cedex, France

关键词: Antithrombin mutant;    Thromboembolism;    Carbohydrate attachment;    Heparin binding;    antithrombin;    antithrombin III;    endo F;    endo-β-N-acetylglucosaminidase F;   

DOI  :  10.1016/0014-5793(88)80183-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A mutant antithrombin was isolated from the plasma of a patient with pulmonary embolism. The new protein, which accounted for 55% of the antithrombin, had decreased heparin affinity and contained two components when analysed on the basis of either charge or molecular mass. Sialidase and endo-β-N-acetylglucosaminidase F treatment suggested that this heterogeneity was due to a partial glycosylation occurring at a new carbohydrate attachment sequence. Peptide mapping by reverse-phase HPLC showed that the abnormality involved the N-terminal tryptic peptide. Sequence analysis demonstrated that the underlying mutation was 7 Ile→Asn which introduces a new Asn-Cys-Thr glycosylation sequence. This new oligosaccharide attachment site occupies the base of the proposed heparin-binding site, and the finding explains the consequent decrease in heparin affinity.

【 授权许可】

Unknown