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dc.contributor.authorCaballero, Gabriel Garcia
dc.contributor.authorBeckwith, Donella
dc.contributor.authorShilova, Nadezhda, V.
dc.contributor.authorGabba, Adele
dc.contributor.authorKutzner, Tanja J.
dc.contributor.authorLudwig, Anna-Kristin
dc.contributor.authorManning, Joachim C.
dc.contributor.authorKaltner, Herbert
dc.contributor.authorSinowatz, Fred
dc.contributor.authorCudic, Mare
dc.contributor.authorBovin, Nicolai, V.
dc.contributor.authorMurphy, Paul V.
dc.contributor.authorGabius, Hans-Joachim
dc.date.accessioned2021-01-08T10:02:18Z
dc.date.available2021-01-08T10:02:18Z
dc.date.issued2020-04-25
dc.identifier.citationGarcía Caballero, Gabriel, Beckwith, Donella, Shilova, Nadezhda V., Gabba, Adele, Kutzner, Tanja J., Ludwig, Anna-Kristin, Manning, Joachim C., Kaltner, Herbert, Sinowatz, Fred, Cudic, Mare, Bovin, Nicolai V., Murphy, Paul V., Gabius, Hans-Joachim. (2020). Influence of protein (human galectin-3) design on aspects of lectin activity. Histochemistry and Cell Biology, 154(2), 135-153. doi:10.1007/s00418-020-01859-9en_IE
dc.identifier.issn0948-6143
dc.identifier.urihttp://hdl.handle.net/10379/16432
dc.description.abstractThe concept of biomedical significance of the functional pairing between tissue lectins and their glycoconjugate counterreceptors has reached the mainstream of research on the flow of biological information. A major challenge now is to identify the principles of structure-activity relationships that underlie specificity of recognition and the ensuing post-binding processes. Toward this end, we focus on a distinct feature on the side of the lectin, i.e. its architecture to present the carbohydrate recognition domain (CRD). Working with a multifunctional human lectin, i.e. galectin-3, as model, its CRD is used in protein engineering to build variants with different modular assembly. Hereby, it becomes possible to compare activity features of the natural design, i.e. CRD attached to an N-terminal tail, with those of homo- and heterodimers and the tail-free protein. Thermodynamics of binding disaccharides proved full activity of all proteins at very similar affinity. The following glycan array testing revealed maintained preferential contact formation with N-acetyllactosamine oligomers and histo-blood group ABH epitopes irrespective of variant design. The study of carbohydrate-inhibitable binding of the test panel disclosed up to qualitative cell-type-dependent differences in sections of fixed murine epididymis and especially jejunum. By probing topological aspects of binding, the susceptibility to inhibition by a tetravalent glycocluster was markedly different for the wild-type vs the homodimeric variant proteins. The results teach the salient lesson that protein design matters: the type of CRD presentation can have a profound bearing on whether basically suited oligosaccharides, which for example tested positively in an array, will become binding partners in situ. When lectin-glycoconjugate aggregates (lattices) are formed, their structural organization will depend on this parameter. Further testing (ga)lectin variants will thus be instrumental (i) to define the full range of impact of altering protein assembly and (ii) to explain why certain types of design have been favored during the course of evolution, besides opening biomedical perspectives for potential applications of the novel galectin forms.en_IE
dc.description.sponsorshipOpen Access funding provided by Projekt DEAL. We gratefully acknowledge inspiring discussions with Drs. B. Friday, A. Leddoz and A. W. L. Nose, valuable input during the review process and generous fnancial support by an NIH Grant (No. CA242351; to M.C.).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherSpringeren_IE
dc.relation.ispartofHistochemistry and cell biologyen
dc.subjectADHESION/GROWTH-REGULATORY GALECTINSen_IE
dc.subjectCARBOHYDRATE-BINDING PROTEIN-35en_IE
dc.subjectOYSTER CRASSOSTREA-VIRGINICAen_IE
dc.subjectNEUROBLASTOMA-CELL-GROWTHen_IE
dc.subjectGLYCAN-BINDINGen_IE
dc.subjectRECOMBINANT POLYPEPTIDEen_IE
dc.subjectSURFACE BINDINGen_IE
dc.subjectGLYCOSYLATIONen_IE
dc.subjectSPECIFICITYen_IE
dc.subjectHISTOCHEMISTSen_IE
dc.titleInfluence of protein (human galectin-3) design on aspects of lectin activityen_IE
dc.typeArticleen_IE
dc.date.updated2021-01-06T19:57:03Z
dc.identifier.doi10.1007/s00418-020-01859-9
dc.local.publishedsourcehttps://doi.org/10.1007/s00418-020-01859-9en_IE
dc.description.peer-reviewedpeer-reviewed
dc.internal.rssid20952289
dc.local.contactPaul Murphy, School Of Chemistry, Room 108, Arts/Science Building, Nui Galway. 2465 Email: paul.v.murphy@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
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