Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling

Ludwig, Anna‐Kristin; Michalak, Malwina; Shilova, Nadezhda V.; André, Sabine; Kaltner, Herbert; Bovin, Nicolai V.; Kopitz, Jürgen; Gabius, Hans‐Joachim

doi:10.3390/molecules22091572

Cited by 11 publications

(7 citation statements)

References 83 publications

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“…This reported difference in binding of Gal-1 and -3 inspired an inverse engineering of the homobivalent Gal-1, i.e., converting WT Gal-1 into a chimera-type–like hybrid composed of the Gal-1 CRD and the NT of Gal-3 (Gal-3NT/1). Strategically, by crossing borders in terms of design and valency, this protein panel fundamentally goes beyond the application of engineering by covalent CRD linkage using various methods and domain transfer among heterobivalent proteins (38–43) as well as linker tailoring (44–47). Our experiments with variants obtained by design-class switching, together with WT proteins as a standard, identify the natural Gal-3 design as a means to attain functional antagonism among galectins.…”

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confidence: 99%

Design–functionality relationships for adhesion/growth-regulatory galectins

Ludwig

Michalak

Xiao

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.

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confidence: 99%

Design–functionality relationships for adhesion/growth-regulatory galectins

Ludwig

Michalak

Xiao

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Prototypal and tandem‐repeat galectins exist as monomers and dimers (known for glycan binding and cell signalling). While prototypal galectins comprise a single CRD, tandem‐repeat galectins contain two distinct CRDs (heterodimeric) separated by a short linker peptide 117 . Chimera‐type galectin also exists as a monomer in solution but is self‐associated to form oligomers participating in glycan binding and protein (such as Alix or Bcl‐2) interactions 118,119 .…”

Section: Prrs In Crustaceansmentioning

confidence: 99%

The role of pattern recognition receptors in crustacean innate immunity

Patnaik

Baliarsingh

Sarkar³

et al. 2023

Reviews in Aquaculture

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Crustacean species are among the most valued seafood with socioeconomic and ecological implications in the global fisheries sector. Microbial infections to the farming stock due to continued expansion and aquaculture puts global crustacean production at risk. Understanding and reviewing the complex innate immune system of crustaceans would be pivotal in formulating informed decisions for the control and management of epidemic diseases, thus making the global crustacean aquaculture industry sustainable. Under the purview of innate immunity in crustaceans, pattern recognition receptors (PRRs) represent the sensors capable of discriminating non‐self pathogenic modules and invoking the activation of immune responses. The immunity to infections can be manifested at cellular (via phagocytosis, apoptosis, nodulation and encapsulation) and humoral (effected by prophenoloxidase cascade, lectins, antimicrobial proteins) levels leading to the elimination of pathogens or subversion of the pathogenic implications. In this review, we discuss the participatory role of 12 types of PRRs identified from crustacean species with an exhaustive focus on structural and functional specificities in binding to pathogens and possible execution of the immune activity. Moreover, we have elaborated on the PRRs‐associated or possible signalling cascades (Toll‐NFκB, IMD‐NFκB and JAK‐STAT) in crustacean species that could bridge our understanding of the resistance or susceptibility of the host to varied pathogenic infections thus providing clues to the regulatory mechanisms involved in pathogenesis of infectious diseases and mechanisms of immunity.

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“…(described in detail below) [22], who tailored a novel sialic acid-binding lectin from an R-type galactose-binding protein using random mutagenesis and a ribosome-display method under the concept of 'natural evolution-mimicry' [23]. Since their work, a significant number of reports of protein engineering base lectin engineering have come out of different laboratories [24][25][26][27][28][29][30][31][32][33][34][35][36]. Aptamer and chemistry-based lectin engineering are also promising and challenging.…”

Section: Current State Of the Art Of Lectin Engineeringmentioning

confidence: 99%

Lectin engineering: the possible and the actual

Hirabayashi

Arai

2019

Interface Focus.

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Lectins are a widespread group of sugar-binding proteins occurring in all types of organisms including animals, plants, bacteria, fungi and even viruses. According to a recent report, there are more than 50 lectin scaffolds (∼Pfam), for which three-dimensional structures are known and sugar-binding functions have been confirmed in the literature, which far exceeds our view in the twentieth century (Fujimoto et al. 2014 Methods Mol. Biol. 1200 , 579–606 ( doi:10.1007/978-1-4939-1292-6_46 )). This fact suggests that new lectins will be discovered either by a conventional screening approach or just by chance. It is also expected that new lectin domains including those found in enzymes as carbohydrate-binding modules will be generated in the future through evolution, although this has never been attempted on an experimental level. Based on the current state of the art, various methods of lectin engineering are available, by which lectin specificity and/or stability of a known lectin scaffold can be improved. However, the above observation implies that any protein scaffold, including those that have never been described as lectins, may be modified to acquire a sugar-binding function. In this review, possible approaches to confer sugar-binding properties on synthetic proteins and peptides are described.

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Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling

Cited by 11 publications

References 83 publications

Design–functionality relationships for adhesion/growth-regulatory galectins

Design–functionality relationships for adhesion/growth-regulatory galectins

The role of pattern recognition receptors in crustacean innate immunity

Lectin engineering: the possible and the actual

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