Applied Biochemistry and Biotechnology

, Volume 165, Issue 3, pp 1037–1046

In silico Analysis of Molecular Mechanisms of Galanthus nivalis Agglutinin-Related Lectin-Induced Cancer Cell Death from Carbohydrate-Binding Motif Evolution Hypothesis

Article

DOI: 10.1007/s12010-011-9318-8

Cite this article as:
Yu, Q., Li, Z., Yao, S. et al. Appl Biochem Biotechnol (2011) 165: 1037. doi:10.1007/s12010-011-9318-8

Abstract

Galanthusnivalis agglutinin-related lectins, a superfamily of strictly mannose-binding-specific lectins widespread amongst monotyledonous plants, have drawn a rising attention for their remarkable anti-proliferative and apoptosis-inducing activities toward various types of cancer cells; however, the precise molecular mechanisms by which they induce tumor cell apoptosis are still only rudimentarily understood. Herein, we found that the three conserved motifs “QXDXNXVXY,” the mannose-specific binding sites, could mutate at one or more amino acid sites, which might be a driving force for the sequential evolution and thus ultimately leading to the complete disappearance of the three conserved motifs. In addition, we found that the motif evolution could result in the diversification of sugar-binding types that G. nivalis agglutinin-related lectins could bind from specific mannose receptors to more types of sugar-containing receptors in cancer cells. Subsequently, we indicated that some sugar-containing receptors such as TNFR1, EGFR, Hsp90, and Hsp70 could block downstream anti-apoptotic or survival signaling pathways, which, in turn, resulted in tumor cell apoptosis. Taken together, our hypothesis that carbohydrate-binding motif evolution may impact the G. nivalis agglutinin-related lectin-induced survival or anti-apoptotic pathways would provide a new perspective for further elucidating the intricate relationships between the carbohydrate-binding specificities and complex molecular mechanisms by which G. nivalis agglutinin-related lectins induce cancer cell death.

Keywords

Galanthus nivalis agglutinin-related lectinEvolutionCancerApoptosisCarbohydrate-binding motif

Supplementary material

12010_2011_9318_MOESM1_ESM.doc (40 kb)
Table S1The present G. nivalis agglutinin-related lectins with one or more mutated motif(s) (DOC 40 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School & School of Life SciencesSichuan UniversityChengduChina