6DBF

Crystal Structure of VHH R303 in complex with InlB-LRR

Summary for 6DBF

• Entry DOI: 10.2210/pdb6dbf/pdb
• Related: 6DBA 6DBD 6DBE
• Descriptor: Listeria virulence factor InlB, InlB specific VHH R303 (3 entities in total)
• Functional Keywords: nanobody vhh listeria internalin, immune system
• Biological source: Listeria monocytogenes; More
• Total number of polymer chains: 2
• Total formula weight: 41464.77

Authors

Brooks, C.L.,Toride King, M.,Huh, I. (deposition date: 2018-05-03, release date: 2018-07-18, Last modification date: 2024-11-06)

Primary citation

King, M.T.,Huh, I.,Shenai, A.,Brooks, T.M.,Brooks, C.L.
Structural basis of VHH-mediated neutralization of the food-borne pathogenListeria monocytogenes.
J. Biol. Chem., 293:13626-13635, 2018

PubMed Abstract: causes listeriosis, a potentially fatal food-borne disease. The condition is especially harmful to pregnant women. outbreaks can originate from diverse foods, highlighting the need for novel strategies to improve food safety. The first step in invasion is internalization of the bacteria, which is mediated by the interaction of the internalin family of virulence factors with host cell receptors. A crucial interaction for invasion of the placenta, and thus a target for therapeutic intervention, is between internalin B (InlB) and the receptor c-Met. Single-domain antibodies (VH, also called nanobodies, or sdAbs) from camel heavy-chain antibodies are a novel solution for preventing infections. The VH R303, R330, and R326 all bind InlB with high affinity; however, the molecular mechanism behind their mode of action was unknown. We demonstrate that despite a high degree of sequence and structural diversity, the VH bind a single epitope on InlB. A combination of gentamicin protection assays and florescent microscopy establish that InlB-specific VH inhibit invasion of HeLa cells. A high-resolution X-ray structure of VH R303 in complex with InlB showed that the VH binds at the c-Met interaction site on InlB, thereby acting as a competitive inhibitor preventing bacterial invasion. These results point to the potential of VH as a novel class of therapeutics for the prevention of listeriosis.

PubMed: 29976754
DOI: 10.1074/jbc.RA118.003888

Experimental method

X-RAY DIFFRACTION (1.55 Å)