6HHU

Structure of the Bacillus anthracis Sap S-layer assembly domain

Summary for 6HHU

• Entry DOI: 10.2210/pdb6hhu/pdb
• Descriptor: S-layer protein sap, nanobody AF684, Nanobody AF694, ... (4 entities in total)
• Functional Keywords: s-layer, exoskeleton, bacterial cell surface, structural protein
• Biological source: Bacillus anthracis; More
• Total number of polymer chains: 3
• Total formula weight: 93968.96

Authors

Remaut, H.,Fioravanti, A. (deposition date: 2018-08-29, release date: 2019-07-24, Last modification date: 2024-10-23)

Primary citation

Fioravanti, A.,Van Hauwermeiren, F.,Van der Verren, S.E.,Jonckheere, W.,Goncalves, A.,Pardon, E.,Steyaert, J.,De Greve, H.,Lamkanfi, M.,Remaut, H.
Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax.
Nat Microbiol, 4:1805-1814, 2019

PubMed Abstract: Anthrax is an ancient and deadly disease caused by the spore-forming bacterial pathogen Bacillus anthracis. At present, anthrax mostly affects wildlife and livestock, although it remains a concern for human public health-primarily for people who handle contaminated animal products and as a bioterrorism threat due to the high resilience of spores, a high fatality rate of cases and the lack of a civilian vaccination programme. The cell surface of B. anthracis is covered by a protective paracrystalline monolayer-known as surface layer or S-layer-that is composed of the S-layer proteins Sap or EA1. Here, we generate nanobodies to inhibit the self-assembly of Sap, determine the structure of the Sap S-layer assembly domain (Sap) and show that the disintegration of the S-layer attenuates the growth of B. anthracis and the pathology of anthrax in vivo. Sap comprises six β-sandwich domains that fold and support the formation of S-layers independently of calcium. Sap-inhibitory nanobodies prevented the assembly of Sap and depolymerized existing Sap S-layers in vitro. In vivo, nanobody-mediated disruption of the Sap S-layer resulted in severe morphological defects and attenuated bacterial growth. Subcutaneous delivery of Sap inhibitory nanobodies cleared B. anthracis infection and prevented lethality in a mouse model of anthrax disease. These findings highlight disruption of S-layer integrity as a mechanism that has therapeutic potential in S-layer-carrying pathogens.

PubMed: 31308522
DOI: 10.1038/s41564-019-0499-1

Experimental method

X-RAY DIFFRACTION (2.7 Å)