The structure of a C. neoformans polysaccharide motif recognized by protective antibodies: A combined NMR and MD study.
The structure of a C. neoformans polysaccharide motif recognized by protective antibodies: A combined NMR and MD study.
复制标题
保护性抗体识别的新型隐球菌多糖基序的结构：NMR 和 MD 联合研究。
DOI：
10.1101/2023.09.06.556507
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Freedberg,DarόnI
中科院分区：
文献类型：
--
作者：
Hargett,AudraA;Azurmendi,HugoF;Crawford,ConorJ;Wear,MaggieP;Oscarson,Stefan;Casadevall,Arturo;Freedberg,DarόnI
Cryptococcus neoformansis a fungal pathogen responsible for cryptococcosis and cryptococcal meningitis. TheC. neoformans’ capsular polysaccharide and its shed exopolysaccharide function both as key virulence factors and to protect the fungal cell from phagocytosis. Currently, a glycoconjugate of these polysaccharides is being explored as a vaccine to protect againstC. neoformansinfection. In this study, NOE andJ-coupling values from NMR experiments were consistent with a converged structure of the synthetic decasaccharide, GXM10-Ac3, calculated from MD simulations. GXM10-Ac3was designed as an extension of glucuronoxylomannan (GXM) polysaccharide motif (M2) which is common in the clinically predominant serotype A strains and is recognized by protective forms of GXM-specific monoclonal antibodies. The M2 motif is a hexasaccharide with a three-residue α-mannan backbone, modified by β-(1→2)-xyloses (Xyl) on the first two mannoses (Man) and a β-(1→2)-glucuronic acid (GlcA) on the third Man. Combined NMR and MD analyses reveal that GXM10-Ac3adopts an extended structure, with Xyl/GlcA branches alternating sides along the α-mannan backbone.O-acetyl esters also alternate sides and are grouped in pairs. MD analysis of a twelve M2-repeating unit polymer supports the notion that the GXM10-Ac3structure is uniformly represented throughout the polysaccharide. This derived GXM model displays high flexibility while maintaining a structural identity, yielding insights to further explore intermolecular interactions between polysaccharides, interactions with anti-GXM mAbs, and the cryptococcal polysaccharide architecture.
