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Title | Cryo-EM reveals the membrane-binding phenomenon of EspB, a virulence factor of the mycobacterial type VII secretion system. |
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Journal, issue, pages | J Biol Chem, Vol. 299, Issue 4, Page 104589, Year 2023 |
Publish date | Mar 6, 2023 |
Authors | Nayanika Sengupta / Surekha Padmanaban / Somnath Dutta / |
PubMed Abstract | Mycobacterium tuberculosis (Mtb) utilizes sophisticated machinery called the type VII secretion system to translocate virulence factors across its complex lipid membrane. EspB, a ∼36 kDa secreted ...Mycobacterium tuberculosis (Mtb) utilizes sophisticated machinery called the type VII secretion system to translocate virulence factors across its complex lipid membrane. EspB, a ∼36 kDa secreted substrate of the ESX-1 apparatus, was shown to cause ESAT-6-independent host cell death. Despite the current wealth of high-resolution structural information of the ordered N-terminal domain, the mechanism of EspB-mediated virulence remains poorly characterized. Here, we document EspB interaction with phosphatidic acid (PA) and phosphatidylserine (PS) in the context of membranes, through a biophysical approach including transmission electron microscopy and cryo-EM. We were also able to show PA, PS-dependent conversion of monomers to oligomers at physiological pH. Our data suggest that EspB adheres to biological membranes with limited PA and PS. EM of yeast mitochondria with EspB indicates a mitochondrial membrane-binding property of this ESX-1 substrate. Further, we determined the 3D structures of EspB with and without PA and observed plausible stabilization of the low complexity C-terminal domain in the presence of PA. Collectively, our cryo-EM-based structural and functional studies of EspB provide further insight into the host-Mtb interaction. |
External links | J Biol Chem / PubMed:36889587 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.5 - 6.6 Å |
Structure data | EMDB-33752: Cryo-EM structure of Mycobacterial Type VII Secretion System Virulence Factor EspB (residues 1-332) with Phosphatidic acid (PA) EMDB-34878: Cryo-EM structure of Mycobacterial Type VII Secretion System Virulence Factor EspB (residues 1-332) |
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