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Taxonomic group: fungi / Basidiomycota (Phylum: Basidiomycota)
Organ / tissue: capsule
Associated disease: infection due to Cryptococcus neoformans [ICD11: XN3EH

]; infection due to Cryptococcus gattii [ICD11: XN0LE

]

NCBI PubMed ID: 33225166
Publication DOI: 10.1021/acsomega.0c04164
Journal NLM ID: 101691658
Publisher: Washington, DC: American Chemical Society
Correspondence: Fu Y <xiaoruoqiu

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Institutions: Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Tianjin, China, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China, Beijing Key Laboratory for Mechanism Study and Precision Diagnosis of Invasive Fungal Diseases, Dynamiker Biotechnology Sub-Center, Tianjin, China

Cryptococcus spp. is an invasive fungal pathogen and causes life-threatening cryptococcosis. Opportunistic cryptococcal infections among the immunocompromised population are mostly caused by Cryptococcus neoformans, whereas the geographical dissemination of Cryptococcus gattii in recent years has threatened lives of even immunocompetent people. The capsule, mainly composed of glucuronoxylomannan (GXM) polysaccharides, plays important roles in the virulence of Cryptococcus spp. The assembling mechanism of GXM polysaccharides into the capsule is little understood because of insufficient experimental data. Molecular modeling and molecular dynamics simulation provide insight into the assembling process. We first built GXM oligosaccharide models of serotypes D, A, B, and C and extracted their secondary structure information from simulation trajectories. All the four mainchains tend to take the nearly twofold helical conformation, whereas peripheral sidechains prefer to form left-handed helices, which are further stabilized by intramolecular hydrogen bonds. Based on the obtained secondary structure information, GXM polysaccharide arrays were built to simulate capsule-assembling processes of C. neoformans and C. gattii using serotypes A and C as representatives, respectively. Trajectory analysis illustrates that electrostatic neutralization of acidic sidechain residues of GXM is a prerequisite for capsule assembling, followed by formation of intermolecular hydrogen bond networks. Further insight into the assembling mechanism of GXM polysaccharides provides the possibility to develop novel treatment and prevention solutions for cryptococcosis.

molecular dynamics, Cryptococcus, Glucuronoxylomannan

Structure type: suggested polymer biological repeating unit
Location inside paper: Fig. 1, c
Trivial name: glucuronoxylomannan (GXM), glucuronoxylomannan
Compound class: CPS, EPS, O-polysaccharide, O-antigen, cell wall polysaccharide, polysaccharide, glucuronoxylomannan, capsule polysaccharide
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_2270799,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72

Methods: molecular modeling, molecular dynamics
3D data: computer modeling, conformation data, dynamics

Related record ID(s): 50832, 50833, 50835
NCBI Taxonomy refs (TaxIDs): 37769
Reference(s) to other database(s): GTC:G42955PN
Show glycosyltransferases

There is only one chemically distinct structure:

*O[C@H]1[C@H](O[C@@H]2OC[C@@H](O)[C@H](O)[C@H]2O)[C@@H](CO)O[C@H](O[C@@H]2[C@H](O[C@@H]3OC[C@@H](O)[C@H](O)[C@H]3O)[C@@H](O[C@H]3[C@H](O)[C@@H](CO)O[C@H](*)[C@H]3O[C@@H]3OC[C@@H](O)[C@H](O)[C@H]3O)O[C@H](CO)[C@H]2O)[C@H]1O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O

SVG MW SMILES 3D mol Ionize