9FVB

Crystal structure of VcSiaP in complex with a VHH antibody (VHH_VcP#2)

Summary for 9FVB

• Entry DOI: 10.2210/pdb9fvb/pdb
• Descriptor: Sialic acid-binding periplasmic protein SiaP, VHH_VcP#2, IMIDAZOLE, ... (6 entities in total)
• Functional Keywords: substrate binding protein, trap transporter, vhh antibody, nanobody, transport protein
• Biological source: Vibrio cholerae; More
• Total number of polymer chains: 4
• Total formula weight: 99742.08

Authors

Schneberger, N.,Hagelueken, G. (deposition date: 2024-06-26, release date: 2024-11-06, Last modification date: 2024-12-04)

Primary citation

Schneberger, N.,Hendricks, P.,Peter, M.F.,Gehrke, E.,Binder, S.C.,Koenig, P.A.,Menzel, S.,Thomas, G.H.,Hagelueken, G.
Allosteric substrate release by a sialic acid TRAP transporter substrate binding protein.
Commun Biol, 7:1559-1559, 2024

PubMed Abstract: The tripartite ATP-independent periplasmic (TRAP) transporters enable Vibrio cholerae and Haemophilus influenzae to acquire sialic acid, aiding their colonization of human hosts. This process depends on SiaP, a substrate-binding protein (SBP) that captures and delivers sialic acid to the transporter. We identified 11 nanobodies that bind specifically to the SiaP proteins from H. influenzae (HiSiaP) and V. cholerae (VcSiaP). Two nanobodies inhibited sialic acid binding. Detailed structural and biophysical studies of one nanobody-SBP complex revealed an allosteric inhibition mechanism, preventing ligand binding and releasing pre-bound sialic acid. A hydrophobic surface pocket of the SBP is crucial for the allosteric mechanism and for the conformational rearrangement that occurs upon binding of sialic acid to the SBP. Our findings provide new clues regarding the mechanism of TRAP transporters, as well as potential starting points for novel drug design approaches to starve these human pathogens of important host-derived molecules.

PubMed: 39580575
DOI: 10.1038/s42003-024-07263-6

Experimental method

X-RAY DIFFRACTION (2.05 Å)