title: Structure of the Complex between a Heparan Sulfate Octasaccharide and Mycobacterial Heparin-Binding Hemagglutinin.
abstract: Heparin-binding hemagglutinin (HBHA) is a 199 amino acid virulence factor at the envelope of Mycobacterium tuberculosis that contributes to latent tuberculosis. The binding of HBHA to respiratory epithelial cells, which leads to extrapulmonary dissemination of the pathogen, is mediated by cell-surface heparan sulfate (HS). We report the structural characterization of the HBHA/HS complex by NMR spectroscopy. To develop a model for the molecular recognition, the first chemically synthesized uniformly13C- and15N-labeled HS octasaccharide and a uniformly13C- and15N-labeled form of HBHA were prepared. Residues 180-195 at the C-terminal region of HBHA show large chemical shift perturbation upon association with the octasaccharide. Molecular dynamics simulations conforming to the multidimensional NMR data revealed key electrostatic and even hydrophobic interactions between the binding partners that may aid in the development of agents targeting the binding event.
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Teng-Yi
authors.initials: TY
authors.lastname: Huang
authors.affiliation: Department of Chemistry, National Dong Hwa University, No. 1, Section 2, Da Hsueh Road, Shoufeng, Hualien, 974, Taiwan.
authors.forename: Deli
authors.initials: D
authors.lastname: Irene
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Medel Manuel L
authors.initials: MM
authors.lastname: Zulueta
authors.affiliation: Department of Chemistry, National Dong Hwa University, No. 1, Section 2, Da Hsueh Road, Shoufeng, Hualien, 974, Taiwan.
authors.forename: Tzu-Jui
authors.initials: TJ
authors.lastname: Tai
authors.affiliation: Department of Chemistry, National Dong Hwa University, No. 1, Section 2, Da Hsueh Road, Shoufeng, Hualien, 974, Taiwan.
authors.forename: Shih-Han
authors.initials: SH
authors.lastname: Lain
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Cheng-Po
authors.initials: CP
authors.lastname: Cheng
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Ping-Xi
authors.initials: PX
authors.lastname: Tsai
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Zhi-Geng
authors.initials: ZG
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Chiao-Chu
authors.initials: CC
authors.lastname: Ku
authors.affiliation: Institute of Molecular Biology, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Chwan-Deng
authors.initials: CD
authors.lastname: Hsiao
authors.affiliation: Department of Chemistry, National Dong Hwa University, No. 1, Section 2, Da Hsueh Road, Shoufeng, Hualien, 974, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chyan
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei, 115, Taiwan.
authors.forename: Shang-Cheng
authors.identifier: 0000-0002-8797-729X
authors.initials: SC
authors.lastname: Hung
mesh_terms: D006497:Heparan Sulfate / Q000737:chemistry*; D037102:Lectins / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry*
chemical_list: D006497:Heparan Sulfate; D037102:Lectins; D009844:Oligosaccharides; C104578:heparin-binding hemagglutinin
keywords: NMR spectroscopy; carbohydrates; heparan sulfate; heparin-binding hemagglutinin; protein structures