| RRC ID |
89133
|
| 著者 |
Chai-Danino M, Ravensary-Modin N, Vladimirov VI, Onyshchuk T, Plöhn M, Barshap ABD, Bsoul A, Peled-Zehavi H, Fluman N.
|
| タイトル |
Membrane-embedded polar residues target membrane proteins for degradation by the quality control protease FtsH.
|
| ジャーナル |
Nat Commun
|
| Abstract |
The biogenesis of membrane proteins (MPs) is inherently error-prone, and is therefore monitored by quality control mechanisms that remove faulty MPs. A key challenge for this surveillance is to recognize misfolded MPs, but how this is achieved remains poorly understood. Here we reveal how FtsH, the main MP quality control protease in Escherichia coli, specifically targets faulty MPs. By analyzing the in vivo degradation of two substrates, we show that lipid-facing polar residues trigger FtsH-mediated degradation. In folded MPs, such polar residues are usually buried in the protein core. Their exposure to the membrane can therefore signal misfolding and promote degradation. Strikingly, lipid-facing polar residues can even trigger degradation of a folded protein, and do not require the extended cytosolic regions typically needed for other FtsH substrates. Recognition depends on the FtsH transmembrane domain and on specific polar residues within it. Thus, sensing misfolding within the membrane helps maintain the integrity of the membrane proteome.
|
| 巻・号 |
17(1)
|
| 公開日 |
2026-2-23
|
| DOI |
10.1038/s41467-026-69829-8
|
| PII |
10.1038/s41467-026-69829-8
|
| PMID |
41730867
|
| PMC |
PMC13039401
|
| MeSH |
ATP-Dependent Proteases* / chemistry
ATP-Dependent Proteases* / genetics
ATP-Dependent Proteases* / metabolism
Cell Membrane* / metabolism
Escherichia coli* / genetics
Escherichia coli* / metabolism
Escherichia coli Proteins* / chemistry
Escherichia coli Proteins* / genetics
Escherichia coli Proteins* / metabolism
Membrane Proteins* / chemistry
Membrane Proteins* / genetics
Membrane Proteins* / metabolism
Protein Folding
Proteolysis
|
| リソース情報 |
| 原核生物(大腸菌) |
|
