Novel polysaccharide binding to the N-terminal tail of galectin-3 is likely modulated by proline isomerization

Michelle C Miller, Kevin H Mayo, Guihua Tai

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8 Scopus citations

Abstract

nteractions between galectins and polysaccharides are crucial to many biological processes, and yet these are some of the least understood, usually being limited to studies with small saccharides and short oligosaccharides. The present study is focused on human galectin-3 (Gal-3) interactions with a 60 kDa rhamnogalacturonan RG-I-4 that we use as a model to garner information as to how galectins interact with large polysaccharides, as well as to develop this agent as a therapeutic against human disease. Gal-3 is unique among galectins, because as the only chimera-type, it has a long N-terminal tail (NT) that has long puzzled investigators due to its dynamic, disordered nature and presence of numerous prolines. Here, we use 15N-1H heteronuclear single quantum coherence NMR spectroscopy to demonstrate that multiple sites on RG-I-4 provide epitopes for binding to three sites on 15N-labeled Gal-3, two within its carbohydrate recognition domain (CRD) and one at a novel site within the NT encompassing the first 40 residues that are highly conserved among all species of Gal-3. Moreover, strong binding of RG-I-4 to the Gal-3 NT occurs on a very slow time scale, suggesting that it may be mediated by cis-trans proline isomerization, a well-recognized modulator of many biological activities. The NT binding epitope within RG-I-4 appears to reside primarily in the side chains of the polysaccharide, some of which are galactans. Our results provide new insight into the role of the NT in Gal-3 function.
Original languageEnglish (US)
Pages (from-to)1038-1051
JournalGlycobiology
Volume27
Issue number11
DOIs
StatePublished - Nov 1 2017

Bibliographical note

Funding Information:
Funding for NMR instrumentation at the University of Minnesota was provided by the Office of the Vice President for Research, the Medical School, the College of Biological Sciences, NIH, NSF and the Minnesota Medical Foundation.

PubMed: MeSH publication types

  • Journal Article

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