9NK6
Thermothelomyces thermophilus SAM complex closed conformation
This is a non-PDB format compatible entry.
Summary for 9NK6
| Entry DOI | 10.2210/pdb9nk6/pdb |
| EMDB information | 49494 |
| Descriptor | Sam35, Sam50, Sam37, ... (4 entities in total) |
| Functional Keywords | membrane protein, beta-barrel, sorting and assembly machinery |
| Biological source | Thermothelomyces thermophilus More |
| Total number of polymer chains | 3 |
| Total formula weight | 147640.45 |
| Authors | Diederichs, K.,Botos, I.,Buchanan, S.K. (deposition date: 2025-02-28, release date: 2025-12-03, Last modification date: 2026-01-07) |
| Primary citation | Diederichs, K.A.,Botos, I.,Hayashi, S.,Gutishvili, G.,Kotov, V.,Kuo, K.,Iinishi, A.,Cooper, G.,Schwarz, B.,Celia, H.,Marlovits, T.C.,Lewis, K.,Gumbart, J.C.,Mindell, J.A.,Buchanan, S.K. The dynamic lateral gate of the mitochondrial beta-barrel biogenesis machinery is blocked by darobactin A. Nat Commun, 16:11349-11349, 2025 Cited by PubMed Abstract: The folding and insertion of β-barrel proteins into the mitochondrial outer membrane is facilitated by the sorting and assembly machinery (SAM) complex. Here we report two 2.8 Å cryo-EM structures of the Thermothelomyces thermophilus SAM complex in the absence of substrate in which the Sam50 lateral gate adopts two different conformations: the first is a closed lateral gate as observed in previously published structures, while the second contains a Sam50 with the first four β-strands rotated outwards by approximately 45°, resulting in an open lateral gate. The observed monomeric open conformation contrasts our previous work where the open conformation was adopted by non-physiological up-down dimers. To understand how these lateral gate dynamics are influenced by substrate, we studied the interaction of the SAM complex with a β-signal peptide mimic, darobactin A. Darobactin A binds to the SAM complex with nanomolar affinity and inhibits the import and assembly of mitochondrial β-barrel proteins in vitro. Lastly, we solved a 3.0 Å cryo-EM structure of the Thermothelomyces thermophilus SAM complex bound to darobactin A, which reveals that darobactin A stabilizes the Sam50 lateral gate similar to the open conformation by binding to strand β1, therefore blocking β-barrel biogenesis. PubMed: 41266328DOI: 10.1038/s41467-025-66417-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.88 Å) |
Structure validation
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