期刊
GLYCOBIOLOGY
卷 24, 期 5, 页码 428-441出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwu008
关键词
circular dichroism; cysteine; galectin-1; molecular dynamics; oxidation
资金
- CSIC-Universidad de la Republica, Uruguay
- National Institutes of Health [R01AI095173]
- Programa de Desarrollo de Ciencias Basicas (PEDECIBA, Uruguay)
- Agencia Nacional de Promocion Cientifica y Tecnologica (Argentina) [PICT 2010-870]
- Universidad de Buenos Aires (Argentina) [UBACYT 20020100100738, UBACYT 20020120100276]
- CONICET (Argentina) [PIP 11220080101207]
- National Multiple Sclerosis Society (USA) [RG 4530A1/1]
- Fundacion Sales/CONICET Program (Argentina)
- Centro de Biologia Estructural del Mercosur (CeBEM)
Galectin-1 (Gal-1), a member of a family of multifunctional lectins, plays key roles in diverse biological processes including cell signaling, immunomodulation, neuroprotection and angiogenesis. The presence of an unusual number of six cysteine residues within Gal-1 sequence prompted a detailed analysis of the impact of the redox environment on the functional activity of this lectin. We examined the role of each cysteine residue in the structure and function of Gal-1 using both experimental and computational approaches. Our results show that: (i) only three cysteine residues present in each carbohydrate recognition domain (CRD) (Cys2, Cys16 and Cys88) were important in protein oxidation, (ii) oxidation promoted the formation of the Cys16Cys88 disulfide bond, as well as multimers through Cys2, (iii) the oxidized protein did not bind to lactose, probably due to poor interactions with Arg48 and Glu71, (iv) in vitro oxidation by air was completely reversible and (v) oxidation by hydrogen peroxide was relatively slow (1.7 +/- 0.2 M-1 s(-1) at pH 7.4 and 25(circle)C). Finally, an analysis of key cysteines in other human galectins is also provided in order to predict their behaviour in response to redox variations. Collectively, our data provide new insights into the structural basis of Gal-1 redox regulation with critical implications in physiology and pathology.
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