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-Structure paper
タイトル | Structure of an endogenous mycobacterial MCE lipid transporter. |
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ジャーナル・号・ページ | Nature, Vol. 620, Issue 7973, Page 445-452, Year 2023 |
掲載日 | 2023年7月26日 |
著者 | James Chen / Alice Fruhauf / Catherine Fan / Jackeline Ponce / Beatrix Ueberheide / Gira Bhabha / Damian C Ekiert / |
PubMed 要旨 | To replicate inside macrophages and cause tuberculosis, Mycobacterium tuberculosis must scavenge a variety of nutrients from the host. The mammalian cell entry (MCE) proteins are important virulence ...To replicate inside macrophages and cause tuberculosis, Mycobacterium tuberculosis must scavenge a variety of nutrients from the host. The mammalian cell entry (MCE) proteins are important virulence factors in M. tuberculosis, where they are encoded by large gene clusters and have been implicated in the transport of fatty acids and cholesterol across the impermeable mycobacterial cell envelope. Very little is known about how cargos are transported across this barrier, and it remains unclear how the approximately ten proteins encoded by a mycobacterial mce gene cluster assemble to transport cargo across the cell envelope. Here we report the cryo-electron microscopy (cryo-EM) structure of the endogenous Mce1 lipid-import machine of Mycobacterium smegmatis-a non-pathogenic relative of M. tuberculosis. The structure reveals how the proteins of the Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the cell envelope. The Mce1 complex is dominated by a curved, needle-like domain that appears to be unrelated to previously described protein structures, and creates a protected hydrophobic pathway for lipid transport across the periplasm. Our structural data revealed the presence of a subunit of the Mce1 complex, which we identified using a combination of cryo-EM and AlphaFold2, and name LucB. Our data lead to a structural model for Mce1-mediated lipid import across the mycobacterial cell envelope. |
リンク | Nature / PubMed:37495693 |
手法 | EM (単粒子) |
解像度 | 2.71 - 3.19 Å |
構造データ | EMDB-29023, PDB-8fed: EMDB-29024, PDB-8fee: EMDB-29025, PDB-8fef: EMDB-29228: Local refinement of MceG in Msmeg Mce1 transporter (Map0a) EMDB-29229: Local refinement of YrbE and MCE ring in Msmeg Mce1 transporter (Map0b) EMDB-29230: Local refinement of MCE ring and needle in Msmeg Mce1 transporter (Map0c) EMDB-29231: Local refinement of MCE needle and portal in Msmeg Mce1 transporter (Map0d) EMDB-29232: Raw, consensus refinement of Msmeg Mce1 transporter (Map0e) EMDB-29233: Local refinement of MceG in Msmeg Mce1-LucB complex (Map1a) EMDB-29234: Local refinement of YrbE, MCE ring, LucB in Msmeg Mce1-LucB complex (Map1b) EMDB-29235: Local refinement of MCE ring and needle in Msmeg Mce1-LucB complex (Map1c) EMDB-29236: Local refinement of MCE needle and portal in Msmeg Mce1-LucB complex (Map1d) EMDB-29237: Raw, consensus refinement of Msmeg Mce1-LucB complex (Map1e) EMDB-29238: Local refinement of MceG in Msmeg Mce1 transporter in the absence of LucB (Map2a) EMDB-29239: Local refinement of YrbE and MCE ring in Msmeg Mce1 transporter in the absence of LucB (Map2b) EMDB-29240: Local refinement of MCE ring and needle in Msmeg Mce1 transporter in the absence of LucB (Map2c) EMDB-29241: Local refinement of MCE needle and portal in Msmeg Mce1 transporter in the absence of LucB (Map2d) EMDB-29242: Raw, consensus refinement of Msmeg Mce1 transporter in the absence of LucB (Map2e) |
化合物 |
ChemComp-UNL: |
由来 |
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キーワード | MEMBRANE PROTEIN / Membrane protein complex / ABC transporter / Virulence factor / Lipid transport |