NMR structure of a fungal virulence factor reveals structural homology with mammalian saposin B

• Published in: Molecular microbiology Vol. 72; no. 2; pp. 344 - 353
• Main Authors: Beck, Moriah R, DeKoster, Gregory T, Cistola, David P, Goldman, William E
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.04.2009; Blackwell Publishing Ltd; Blackwell
• Subjects: Amino Acid Sequence; Bacterial proteins; Binding sites; Biological and medical sciences; Calcium-Binding Proteins - chemistry; Dimerization; Fundamental and applied biological sciences. Psychology; Fungal Proteins - chemistry; Fungi; Histoplasma - chemistry; Histoplasma capsulatum; Lipids; Microbiology; Models, Molecular; Molecular Sequence Data; NMR; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Protein Binding; Protein Conformation; Saposins - chemistry; Virology; Virulence Factors - chemistry; Vertebrata; Mammalia; Microbiology; Virulence; Glycoprotein; Homology; NMR spectrometry
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2009.06647.x

The fungal protein CBP ( calcium binding protein) is a known virulence factor with an unknown virulence mechanism. The protein was identified based on its ability to bind calcium and its prevalence as Histoplasma capsulatum's most abundant secreted protein. However, CBP has no sequence homology with other CBPs and contains no known calcium binding motifs. Here, the NMR structure of CBP reveals a highly intertwined homodimer and represents the first atomic level NMR model of any fungal virulence factor. Each CBP monomer is comprised of four α-helices that adopt the saposin fold, characteristic of a protein family that binds to membranes and lipids. This structural homology suggests that CBP functions as a lipid binding protein, potentially interacting with host glycolipids in the phagolysosome of host cells.