Crystal structure of the fibrinogen-like recognition domain of FIBCD1

Jesper Bonnet Møller, Anders Schlosser, Grith Lykke Sørensen, I Burns, T.J Greenhough, Uffe Holmskov, Anette K Shrive

Research output: Contribution to conference without publisher/journalPosterResearchpeer-review

Abstract

The high resolution crystal structures of a recombinant fragment of the C-terminal fibrinogen-related domain of FIBCD1, a vertebrate chitin receptor, have been determined. The overall structure shows similarity in structure and aggregation to the homologous innate immune protein tachylectin 5A. Binding of one of its high affinity ligands, ManNAc, in the S1 site shows that the predominant interaction is via the acetyl group with the oxygen interacting with two main chain NH groups, the acetamide nitrogen interacting with the side chain of Tyr431 and the methyl group inserted in to a hydrophobic pocket. There is very little change between native and ligand bound, the most notable being a shift in orientation of Tyr431. In the native structure, a crystal contact results in one of the independent protomers binding the first GlcNAc of the Asn340 N-linked glycan on the other independent protomer, shedding light on the mode of binding of chitin itself. In the ligand bound structure the GlcNAc is replaced by the higher affinity ligand ManNAc. The binding of the ManNAc pyranose ring differs markedly between the two independent subunits but in all structures the binding of the N-acetyl group is conserved. In addition, a sulphate ion has been modelled into the electron density at a location similar to the S3 binding site in L-ficolin.

Original languageEnglish
Publication date9. Mar 2012
Number of pages1
Publication statusPublished - 9. Mar 2012
EventKeystone Symposia - Innate Immunity: Sensing the Microbes and Damage Signals - Keystone, Colorado, United States
Duration: 4. Mar 20129. Mar 2012

Conference

ConferenceKeystone Symposia - Innate Immunity: Sensing the Microbes and Damage Signals
Country/TerritoryUnited States
CityKeystone, Colorado
Period04/03/201209/03/2012

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