8A0C

Capsular polysaccharide synthesis multienzyme in complex with CMP

Summary for 8A0C

• Entry DOI: 10.2210/pdb8a0c/pdb
• Descriptor: Bcs3, PHOSPHATE ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: bacterial capsule synthesis, biosynthetic protein
• Biological source: Haemophilus influenzae
• Total number of polymer chains: 2
• Total formula weight: 276932.04

Authors

Cifuente, J.O.,Schulze, J.,Bethe, A.,Di Domenico, V.,Litschko, C.,Budde, I.,Eidenberger, L.,Thiesler, H.,Ramon-Roth, I.,Berger, M.,Claus, H.,DAngelo, C.,Marina, A.,Gerardy-Schahn, R.,Schubert, M.,Guerin, M.E.,Fiebig, T. (deposition date: 2022-05-27, release date: 2023-04-26, Last modification date: 2024-05-01)

Primary citation

Cifuente, J.O.,Schulze, J.,Bethe, A.,Di Domenico, V.,Litschko, C.,Budde, I.,Eidenberger, L.,Thiesler, H.,Ramon Roth, I.,Berger, M.,Claus, H.,D'Angelo, C.,Marina, A.,Gerardy-Schahn, R.,Schubert, M.,Guerin, M.E.,Fiebig, T.
A multi-enzyme machine polymerizes the Haemophilus influenzae type b capsule.
Nat.Chem.Biol., 19:865-877, 2023

PubMed Abstract: Bacterial capsules have critical roles in host-pathogen interactions. They provide a protective envelope against host recognition, leading to immune evasion and bacterial survival. Here we define the capsule biosynthesis pathway of Haemophilus influenzae serotype b (Hib), a Gram-negative bacterium that causes severe infections in infants and children. Reconstitution of this pathway enabled the fermentation-free production of Hib vaccine antigens starting from widely available precursors and detailed characterization of the enzymatic machinery. The X-ray crystal structure of the capsule polymerase Bcs3 reveals a multi-enzyme machine adopting a basket-like shape that creates a protected environment for the synthesis of the complex Hib polymer. This architecture is commonly exploited for surface glycan synthesis by both Gram-negative and Gram-positive pathogens. Supported by biochemical studies and comprehensive 2D nuclear magnetic resonance, our data explain how the ribofuranosyltransferase CriT, the phosphatase CrpP, the ribitol-phosphate transferase CroT and a polymer-binding domain function as a unique multi-enzyme assembly.

PubMed: 37277468
DOI: 10.1038/s41589-023-01324-3

Experimental method

X-RAY DIFFRACTION (2.9 Å)