Macromolecular assemblies of complex polysaccharides with galectin-3 and their synergistic effects on function

Tao Zhang, Michelle C. Miller, Yi Zheng, Zhongyu Zhang, Huiting Xue, Dongyang Zhao, Jiyong Su, Kevin H. Mayo, Yifa Zhou, Guihua Tai

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Although pectin-derived polysaccharides can antagonize galectin function in various pathological disorders, the nature of their binding interactions needs to be better defined for developing them as drugs. Moreover, given their relatively large size and complexity, pectin-derived polysaccharides are also useful as model systems to assess inter-polysaccharide and protein–polysaccharide interactions. Here, we investigated interactions between galectin-3 (Gal-3) and pectin-derived polysaccharides: a rhamnogalacturonan (RG) and two homogalacturonans (HGs). BioLayer Interferometry and fluorescence-linked immunosorbent assays indicate that these polysaccharides bind Gal-3 with macroscopic or apparent KD values of 49 nM, 46 μM, and 138 μM, respectively. 15N-1H heteronuclear single quantum coherence (HSQC) NMR studies reveal that these polysaccharides interact primarily with the F-face of the Gal-3 carbohydrate recognition domain. Even though their binding to Gal-3 does not inhibit Gal-3-mediated T-cell apoptosis and only weakly attenuates hemagglutination, their combination in specific proportions increases activity synergistically along with avidity for Gal-3. This suggests that RG and HG polysaccharides act in concert, a proposal supported by polysaccharide particle size measurements and 13C-1H HSQC data. Our model has HG interacting with RG to promote increased avidity of RG for Gal-3, likely by exposing additional lectin-binding sites on the RG. Overall, the present study contributes to our understanding of how complex HG and RG polysaccharides interact with Gal-3.

Original languageEnglish (US)
Pages (from-to)3849-3868
Number of pages20
JournalBiochemical Journal
Volume474
Issue number22
DOIs
StatePublished - Nov 15 2017

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China [nos 31370805 and 31470798] and the Fundamental Research Funds for the Central Universities. The NMR instrumentation was provided by funds from the US National Science Foundation [BIR-961477], the University of Minnesota Medical School, and the Minnesota Medical Foundation.

Publisher Copyright:
© 2017 The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

Fingerprint

Dive into the research topics of 'Macromolecular assemblies of complex polysaccharides with galectin-3 and their synergistic effects on function'. Together they form a unique fingerprint.

Cite this