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Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains

Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains
Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains
The carbohydrate recognition domains (CRDs) of lung collectin surfactant protein D (SP-D) recognize sugar patterns on the surface of lung pathogens and promote phagocytosis. Using Haemophilus influenzae Eagan strains expressing well-characterized lipopolysaccharide (LPS) surface structures of various levels of complexity, we show that bacterial recognition and binding by SP-D is inversely related to LPS chain extent and complexity. The crystal structure of a biologically active recombinant trimeric SP-D CRD complexed with a delipidated Eagan 4A LPS suggests that efficient LPS recognition by SP-D requires multiple binding interactions utilizing the three major ligand-binding determinants in the SP-D binding pocket, with Ca-dependent binding of inner-core heptose accompanied by interaction of anhydro-Kdo (4,7-anhydro-3-deoxy-d-manno-oct-2-ulosonic acid) with Arg343 and Asp325. Combined with enzyme-linked immunosorbent assays (ELISAs) and fluorescence-activated cell sorter (FACS) binding analyses, our results show that extended LPS structures previously thought to be targets for collectins are important in shielding the more vulnerable sites in the LPS core, revealing a mechanism by which pathogens with complex LPS extensions efficiently evade a first-line mucosal innate immune defense. The structure also reveals for the first time the dominant form of anhydro-Kdo.
0019-9567
1585-1592
Clark, Howard W.
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Mackay, Rose-Marie
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Deadman, Mary E
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Hood, Derek W
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Madsen, Jens
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Moxon, E. Richard
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Townsend, J. Paul
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Reid, Kenneth B.M.
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Ahmed, Abdul
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Shaw, Amy J.
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Greenhough, Trevor J.
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Shrive, Annette K.
230ea5a6-89e7-47ed-9dac-4cd9847f9bc6
Clark, Howard W.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Mackay, Rose-Marie
19cf1b92-c65d-4baa-a165-ab630bf77ec3
Deadman, Mary E
081e4f50-c07b-440a-874e-da96eaeaabb3
Hood, Derek W
1cc0e2ce-cf18-4890-884a-7e6833152fb7
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Moxon, E. Richard
5ce688e1-52bf-4a89-b125-a6183dd09ac6
Townsend, J. Paul
16c04a59-d07b-4d3d-9b07-be35529bc024
Reid, Kenneth B.M.
74c6c3e3-d682-446d-b159-b635e6056e4e
Ahmed, Abdul
40ef4732-eee9-48a7-ad79-586b360fd878
Shaw, Amy J.
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Greenhough, Trevor J.
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Shrive, Annette K.
230ea5a6-89e7-47ed-9dac-4cd9847f9bc6

Clark, Howard W., Mackay, Rose-Marie, Deadman, Mary E, Hood, Derek W, Madsen, Jens, Moxon, E. Richard, Townsend, J. Paul, Reid, Kenneth B.M., Ahmed, Abdul, Shaw, Amy J., Greenhough, Trevor J. and Shrive, Annette K. (2016) Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains. Infection and Immunity, 84 (5), 1585-1592. (doi:10.1128/IAI.01239-15). (PMID:26953329)

Record type: Article

Abstract

The carbohydrate recognition domains (CRDs) of lung collectin surfactant protein D (SP-D) recognize sugar patterns on the surface of lung pathogens and promote phagocytosis. Using Haemophilus influenzae Eagan strains expressing well-characterized lipopolysaccharide (LPS) surface structures of various levels of complexity, we show that bacterial recognition and binding by SP-D is inversely related to LPS chain extent and complexity. The crystal structure of a biologically active recombinant trimeric SP-D CRD complexed with a delipidated Eagan 4A LPS suggests that efficient LPS recognition by SP-D requires multiple binding interactions utilizing the three major ligand-binding determinants in the SP-D binding pocket, with Ca-dependent binding of inner-core heptose accompanied by interaction of anhydro-Kdo (4,7-anhydro-3-deoxy-d-manno-oct-2-ulosonic acid) with Arg343 and Asp325. Combined with enzyme-linked immunosorbent assays (ELISAs) and fluorescence-activated cell sorter (FACS) binding analyses, our results show that extended LPS structures previously thought to be targets for collectins are important in shielding the more vulnerable sites in the LPS core, revealing a mechanism by which pathogens with complex LPS extensions efficiently evade a first-line mucosal innate immune defense. The structure also reveals for the first time the dominant form of anhydro-Kdo.

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Accepted/In Press date: 3 March 2016
e-pub ahead of print date: 7 March 2016
Published date: May 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 395456
URI: https://eprints.soton.ac.uk/id/eprint/395456
ISSN: 0019-9567
PURE UUID: 73f95201-6a8a-430e-9d02-a6f7bc8220db
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

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Date deposited: 31 May 2016 09:22
Last modified: 09 Dec 2019 19:36

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Contributors

Author: Howard W. Clark
Author: Rose-Marie Mackay ORCID iD
Author: Mary E Deadman
Author: Derek W Hood
Author: Jens Madsen ORCID iD
Author: E. Richard Moxon
Author: J. Paul Townsend
Author: Kenneth B.M. Reid
Author: Abdul Ahmed
Author: Amy J. Shaw
Author: Trevor J. Greenhough
Author: Annette K. Shrive

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