The structure-function relationship analysis of VEGI: Y111 is an important residue in biological activity
- VernacularTitle:Y111是维持血管内皮细胞生长抑制因子生物活性的关键氨基酸
- Author:
Min ZHANG
;
Jingjuan YAO
;
Xin PAN
;
Wei PAN
;
Zhongtian QI
- Publication Type:Journal Article
- Keywords:
VEGI;
endothelial cells;
site-directed mutagenesis;
biological activity
- From:
Chinese Pharmacological Bulletin
1987;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim Vascular endothelial cell growth inhibitor(VEGI) is a recently discovered novel member of the TNF superfamily,which is expressed predominantly in endothelial cells.As an endothelial cell-specific negative regulator of angiogenesis,the relationship between structure and function of VEGI is not understood at present.Methods In order to explore the functional key amino acids of VEGI,four mutants of VEGI(E45→R,G47→A,Y111→F,Y111→T) were construced by site-directed mutagenesis,and recombinant proteins were generated from E.coli.Four mutant proteins behaved similar to the wild type VEGI in various physico-chemical assays.The proliferation of HUVEC and chick choriallantic membrane assay were performed to study the activity of four mutants.Results The mutant E45→R significantly decreased the biological activity,and the mutant G47→A caused a slight drop on activity,but the mutants Y111→F,Y111→T almost completely abolished biological activity.Conclusion It suggests that Y111 is an important residue in biological activity,which may play a direct role in receptor recognition.Moreover,the tyrosine ring and hydroxy group of the amino acid are important determinant of biological activity.Additionally,E45 also plays an important role in biological activity of VEGI.
