7DM2

crystal structure of the M. tuberculosis phosphate ABC transport receptor PstS-1 in complex with Fab p4-170

Summary for 7DM2

• Entry DOI: 10.2210/pdb7dm2/pdb
• Descriptor: Phosphate-binding protein PstS 1, light chain, heavy chain, ... (5 entities in total)
• Functional Keywords: antibody, complex, transport protein, transport protein-immune system complex, transport protein/immune system
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 3
• Total formula weight: 84981.27

Authors

Ma, B.,Freund, N.,Xiang, Y. (deposition date: 2020-12-01, release date: 2020-12-23, Last modification date: 2024-10-16)

Primary citation

Watson, A.,Li, H.,Ma, B.,Weiss, R.,Bendayan, D.,Abramovitz, L.,Ben-Shalom, N.,Mor, M.,Pinko, E.,Bar Oz, M.,Wang, Z.,Du, F.,Lu, Y.,Rybniker, J.,Dahan, R.,Huang, H.,Barkan, D.,Xiang, Y.,Javid, B.,Freund, N.T.
Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis.
Nat Commun, 12:602-602, 2021

PubMed Abstract: Mycobacterium tuberculosis (Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses during active infection. The antibodies, members of four distinct B cell clones, are directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4-36 and p4-163 reduce Mycobacterium bovis-BCG and Mtb levels in an ex vivo human whole blood growth inhibition assay in an FcR-dependent manner; meanwhile, germline versions of p4-36 and p4-163 do not bind Mtb. Crystal structures of p4-36 and p4-170, complexed to PstS1, are determined at 2.1 Å and 2.4 Å resolution, respectively, to reveal two distinctive PstS1 epitopes. Lastly, a prophylactic p4-36 and p4-163 treatment in Mtb-infected Balb/c mice reduces bacterial lung burden by 50%. Our study shows that inhibitory anti-PstS1 B cell responses arise during active tuberculosis.

PubMed: 33504803
DOI: 10.1038/s41467-021-20930-0

Experimental method

X-RAY DIFFRACTION (2.4 Å)