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Structural definition of hSP-D recognition of Salmonella enterica LPS inner core oligosaccharides reveals alternative binding modes for the same LPS

Structural definition of hSP-D recognition of Salmonella enterica LPS inner core oligosaccharides reveals alternative binding modes for the same LPS
Structural definition of hSP-D recognition of Salmonella enterica LPS inner core oligosaccharides reveals alternative binding modes for the same LPS
The crystal structures of a biologically and therapeutically active recombinant homotrimeric fragment of native human SP-D (hSP-D) complexed with the inner core oligosaccharide of the Salmonella enterica sv Minnesota rough strains R5 and R7 (rough mutant chemotypes Rc and Rd1) have been determined. The structures reveal that hSP-D specifically and preferentially targets the LPS inner core via the innermost conserved Hep-Kdo pair with the flexibility for alternative recognition when this preferred epitope is not available for binding. Hep-Kdo binding is achieved through calcium dependent recognition of the heptose dihydroxyethyl side chain coupled with specific interactions between the Kdo and the binding site flanking residues Arg343 and Asp325 with evidence for an extended binding site for LPS inner cores containing multiple Kdo residues. In one subunit of the R5-bound structure this preferred mode of binding is precluded by the crystal lattice and oligosaccharide is bound through the terminal inner core glucose. The structures presented here thus provide unique multiple insights into the recognition and binding of bacterial LPS by hSP-D. Not only is it demonstrated that hSP-D targets the highly conserved LPS proximal inner core Hep-Kdo motif, but also that hSP-D can recognise either terminal or non-terminal sugars and has the flexibility and versatility to adopt alternative strategies for bacterial recognition, utilising alternative LPS epitopes when the preferred inner core Hep-Kdo disaccharide is not available for binding.
SP-D, innate immunity, Salmonella, crystalstructure
1932-6203
Littlejohn, Jamie R.
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da Silva, Ruben F.
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Neale, William A.
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Smallcombe, Carrie C.
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Clark, Howard
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Mackay, Rose-Marie
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Watson, Alastair S.
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Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Hood, Derek W.
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Burns, Ian
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Greenhough, Trevor J.
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Shrive, Annette K.
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Littlejohn, Jamie R.
c472d3af-8f97-4e65-8d1e-1e076e2a52a3
da Silva, Ruben F.
8325f0a5-f202-4b3f-85b5-b58a8cfe588b
Neale, William A.
cb0a1e05-e316-4ac5-8159-8c5203bc3696
Smallcombe, Carrie C.
3da9d060-1336-48a5-a128-1b6763b4e6f2
Clark, Howard
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Mackay, Rose-Marie
19cf1b92-c65d-4baa-a165-ab630bf77ec3
Watson, Alastair S.
6f3beb19-7e9d-4aa9-99d8-beb24c61588a
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Hood, Derek W.
f9ec1f2c-0867-4cc3-8157-1f739cb1f774
Burns, Ian
859860b3-27e8-4471-82f1-a0ae0ec8c842
Greenhough, Trevor J.
16f759d0-9935-4a90-bdc6-a30e69f87f78
Shrive, Annette K.
298b7952-102c-443b-86e7-e83e4814da84

Littlejohn, Jamie R., da Silva, Ruben F., Neale, William A., Smallcombe, Carrie C., Clark, Howard, Mackay, Rose-Marie, Watson, Alastair S., Madsen, Jens, Hood, Derek W., Burns, Ian, Greenhough, Trevor J. and Shrive, Annette K. (2018) Structural definition of hSP-D recognition of Salmonella enterica LPS inner core oligosaccharides reveals alternative binding modes for the same LPS. PLoS ONE. (doi:10.1371/journal.pone.0199175).

Record type: Article

Abstract

The crystal structures of a biologically and therapeutically active recombinant homotrimeric fragment of native human SP-D (hSP-D) complexed with the inner core oligosaccharide of the Salmonella enterica sv Minnesota rough strains R5 and R7 (rough mutant chemotypes Rc and Rd1) have been determined. The structures reveal that hSP-D specifically and preferentially targets the LPS inner core via the innermost conserved Hep-Kdo pair with the flexibility for alternative recognition when this preferred epitope is not available for binding. Hep-Kdo binding is achieved through calcium dependent recognition of the heptose dihydroxyethyl side chain coupled with specific interactions between the Kdo and the binding site flanking residues Arg343 and Asp325 with evidence for an extended binding site for LPS inner cores containing multiple Kdo residues. In one subunit of the R5-bound structure this preferred mode of binding is precluded by the crystal lattice and oligosaccharide is bound through the terminal inner core glucose. The structures presented here thus provide unique multiple insights into the recognition and binding of bacterial LPS by hSP-D. Not only is it demonstrated that hSP-D targets the highly conserved LPS proximal inner core Hep-Kdo motif, but also that hSP-D can recognise either terminal or non-terminal sugars and has the flexibility and versatility to adopt alternative strategies for bacterial recognition, utilising alternative LPS epitopes when the preferred inner core Hep-Kdo disaccharide is not available for binding.

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Accepted/In Press date: 2 June 2018
e-pub ahead of print date: 18 June 2018
Published date: 18 June 2018
Keywords: SP-D, innate immunity, Salmonella, crystalstructure

Identifiers

Local EPrints ID: 422403
URI: http://eprints.soton.ac.uk/id/eprint/422403
ISSN: 1932-6203
PURE UUID: 564d3238-2b55-46fb-b62a-d9e13efa3422
ORCID for Rose-Marie Mackay: ORCID iD orcid.org/0000-0002-9493-9654
ORCID for Jens Madsen: ORCID iD orcid.org/0000-0003-1664-7645

Catalogue record

Date deposited: 23 Jul 2018 16:30
Last modified: 26 Nov 2021 02:52

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Contributors

Author: Jamie R. Littlejohn
Author: Ruben F. da Silva
Author: William A. Neale
Author: Carrie C. Smallcombe
Author: Howard Clark
Author: Rose-Marie Mackay ORCID iD
Author: Alastair S. Watson
Author: Jens Madsen ORCID iD
Author: Derek W. Hood
Author: Ian Burns
Author: Trevor J. Greenhough
Author: Annette K. Shrive

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