Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.754789
Title: Structural characterisation of oligosaccharide recognition by surfactant protein D
Author: Littlejohn, Jamie Reginald
ISNI:       0000 0004 7427 8099
Awarding Body: Keele University
Current Institution: Keele University
Date of Award: 2018
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Abstract:
Human surfactant protein D (hSP-D) is a C-type lectin and member of the collectin family that is involved in pathogen recognition as part of the innate immune response. Recognition occurs through the carbohydrate arrays on the surfaces of the pathogens. This work focuses on characterising, at the atomic level, the recognition of oligosaccharide analogues of the carbohydrate arrays using a recombinant fragment of human surfactant protein D (rfhSP-D). The crystal structures of three rfhSP-D complexes with the α(1→6)-linked isomaltotriose, β(1→4)-linked cellotriose and β(1→3)-linked laminaritriose have been successfully solved in P21 using rigid body refinement. Isomaltotriose was refined to 1.96Å with refinement statistics: Rwork 0.1664 and Rfree 0.2084. Cellotriose was refined to 1.59Å with refinement statistics: Rwork 0.0.1879 and Rfree 0.2106. Laminaritriose was refined to 1.75Å with refinement statistics: Rwork 0.1808 and Rfree 0.2193. In combination with two previously solved malto-N-ose complexes, the structures reveal a new binding mechanism for β-D-glucoses in SP-D and identify a new extended binding surface. The crystal structure of rfhSP-D in complex with the disaccharide unit of peptidoglycan, muramyl disaccharide, extracted from the gram-positive bacteria, Micrococcus luteus has been solved in P21 and refined to 1.95Å with final refinement statistics of Rwork 0.1708 and Rfree 0.2169. This crystal structure provides the first insight into recognition of peptidoglycan, an important part of the bacterial cell wall. The rfhSP-D complex with the R7 rough mutant oligosaccharide from S. enterica minnesota has been redetermined from previous work in the group. The structure has been solved in P21 and refined to 1.75Å with final refinement statistics of Rwork 0.1730 and Rfree 0.1960. The crystal structure, along with the known R5 oligosaccharide complex, builds on the understanding of the flexibility and versatility of lipopolysaccharide recognition by hSP-D and the important role of the two flanking residues, Asp325 and Arg343.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.754789  DOI: Not available
Keywords: Q Science (General)
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