Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086

被引：64

作者：

Mascioni, Alessandro

Bentley, Breagh E. ^{[2
]}

Camarda, Rosaria ^{[2
]}

Dilts, Deborah A. ^{[2
]}

Fink, Pamela ^{[2
]}

Gusarova, Viktoria ^{[2
]}

Hoiseth, Susan K. ^{[2
]}

Jacob, Jaison ^{[1
]}

Lin, Shuo L. ^{[2
]}

Malakian, Karl ^{[1
]}

McNeil, Lisa K. ^{[2
]}

Mininni, Terri ^{[2
]}

Moy, Franklin ^{[1
]}

Murphy, Ellen ^{[2
]}

Novikova, Elena ^{[2
]}

Sigethy, Scott ^{[2
]}

Wen, Yingxia

Zlotnick, Gary W. ^{[2
]}

Tsao, Desiree H. H. ^{[1
]}

机构：

[1] Wyeth Res, Struct Biol & Computat Chem, Cambridge, MA 02140 USA

[2] Wyeth Vaccines Res, Pearl River, NY 10965 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 13期

关键词：

NUCLEAR MAGNETIC-RESONANCE; B NEISSERIA-MENINGITIDIS; ALTERNATIVE CONFORMATIONS; ANTIBODY COMPLEXES; NMR-SPECTROSCOPY; CHEMICAL-SHIFT; SEROGROUP-B; PROTEIN; LIPOPROTEIN; ANTIGEN;

D O I：

10.1074/jbc.M808831200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

LP2086 is a family of outer membrane lipoproteins from Neisseria meningitidis, which elicits bactericidal antibodies and are currently undergoing human clinical trials in a bivalent formulation where each antigen represents one of the two known LP2086 subfamilies. Here we report the NMR structure of the recombinant LP2086 variant B01, a representative of the LP2086 subfamily B. The structure reveals a novel fold composed of two domains: a "taco-shaped" N-terminal beta-sheet and a C-terminal beta-barrel connected by a linker. The structure in micellar solution is consistent with a model of LP2086 anchored to the outer membrane bilayer through its lipidated N terminus. A long flexible chain connects the folded part of the protein to the lipid anchor and acts as spacer, making both domains accessible to the host immune system. Antibodies broadly reactive against members from both subfamilies have been mapped to the N terminus. A surface of subfamily-defining residues was identified on one face of the protein, offering an explanation for the induction of subfamily-specific bactericidal antibodies.

引用

页码：8729 / 8737

页数：9

共 39 条

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