+
Open data
-
Basic information
Entry | Database: PDB / ID: 9mr4 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | NAC: Ribosome nascent chain complex(Oxa1L) | |||||||||
![]() |
| |||||||||
![]() | RIBOSOME / NAC / mitochondrial sorting | |||||||||
Function / homology | ![]() negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / positive regulation of cell proliferation involved in heart morphogenesis / positive regulation of skeletal muscle tissue growth / cardiac ventricle development / heart trabecula morphogenesis / skeletal muscle tissue regeneration / ribosomal subunit ...negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / positive regulation of cell proliferation involved in heart morphogenesis / positive regulation of skeletal muscle tissue growth / cardiac ventricle development / heart trabecula morphogenesis / skeletal muscle tissue regeneration / ribosomal subunit / laminin receptor activity / ubiquitin ligase inhibitor activity / positive regulation of signal transduction by p53 class mediator / 90S preribosome / phagocytic cup / protein-RNA complex assembly / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / laminin binding / translation regulator activity / gastrulation / MDM2/MDM4 family protein binding / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / wound healing / spindle / rRNA processing / antimicrobial humoral immune response mediated by antimicrobial peptide / rhythmic process / positive regulation of canonical Wnt signaling pathway / protein transport / heparin binding / large ribosomal subunit / regulation of translation / ribosome binding / virus receptor activity / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / small ribosomal subunit rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / perikaryon / defense response to Gram-negative bacterium / cytosolic large ribosomal subunit / killing of cells of another organism / in utero embryonic development / cytoplasmic translation / cell differentiation / transcription coactivator activity / tRNA binding / mitochondrial inner membrane / negative regulation of translation / postsynaptic density / rRNA binding / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / cell division / DNA repair / mRNA binding / apoptotic process / synapse / dendrite / centrosome / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / Golgi apparatus / positive regulation of transcription by RNA polymerase II / DNA binding / RNA binding / extracellular exosome / zinc ion binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.65 Å | |||||||||
![]() | Maldosevic, E. / Jomaa, A. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: A molecular switch in NAC prevents mitochondrial protein mistargeting by SRP. Authors: Emir Maldosevic / Radoslaw Gora / Liangguang Leo Lin / Linyao Elina Zhou / Zexin Jason Li / Yelena Peskova / Ling Qi / Shu-Ou Shan / Ahmad Jomaa Abstract: The nascent polypeptide-associated complex (NAC) co-translationally screens all nascent proteins and regulates their access to the signal recognition particle (SRP) to ensure the fidelity of protein ...The nascent polypeptide-associated complex (NAC) co-translationally screens all nascent proteins and regulates their access to the signal recognition particle (SRP) to ensure the fidelity of protein targeting to the endoplasmic reticulum (ER). However, the mechanism by which NAC prevents the mistargeting of nascent mitochondrial proteins remains unclear. Here, we identified a molecular switch in NAC that allows its central barrel domain to adopt a stabilized conformation on ribosomes exposing a mitochondrial targeting sequence (MTS). Mutations of the MTS on the nascent chain or in the NAC switch region increases NAC barrel dynamics and reduces its binding to the ribosome. This leads to an impaired ability of NAC to prevent mistargeting by SRP and causes ER stress in human cells. Our work reveals how NAC detects nascent mitochondrial proteins early in translation and prevents their promiscuous access to SRP, elucidating the structural basis that underlies this role and providing novel insights into protein targeting fidelity with broader implications for cellular proteostasis. | |||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 5.2 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.4 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 2.7 MB | Display | |
Data in XML | ![]() | 382.1 KB | Display | |
Data in CIF | ![]() | 629 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 48552MC ![]() 71286 ![]() 71287 M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
+Protein , 28 types, 28 molecules m69FTWXYcdfhlpqrSSWWUUKKIIPPGGVVOOLLEFEG
-Ribosomal protein ... , 14 types, 14 molecules 0ABJNVjwyDDEEQQTTFF
#2: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#7: Protein | Mass: 28088.863 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#8: Protein | Mass: 46107.977 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#15: Protein | Mass: 20288.465 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#19: Protein | Mass: 24207.285 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 14892.505 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#40: Protein | Mass: 11111.032 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#50: Protein | Mass: 26715.344 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: G1TNM3, DNA-(apurinic or apyrimidinic site) lyase |
#58: Protein | Mass: 22913.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#61: Protein | Mass: 22641.564 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#63: Protein | Mass: 18468.826 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#65: Protein | Mass: 17259.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#74: Protein | Mass: 14865.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#80: Protein | Mass: 7855.052 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-RNA chain , 6 types, 6 molecules 47K258
#3: RNA chain | Mass: 1892.173 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#5: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#16: RNA chain | Mass: 548040.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#53: RNA chain | Mass: 24414.496 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#54: RNA chain | Mass: 1148115.375 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#55: RNA chain | Mass: 50143.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-60S ribosomal protein ... , 9 types, 9 molecules CGHIMZagE
#9: Protein | Mass: 46388.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#12: Protein | Mass: 36267.605 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#13: Protein | Mass: 21871.418 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#14: Protein | Mass: 24643.057 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#18: Protein | Mass: 23870.549 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#31: Protein | Mass: 15835.831 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#32: Protein | Mass: 16620.561 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#37: Protein | Mass: 13326.074 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#56: Protein | Mass: 33028.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Large ribosomal subunit protein ... , 13 types, 13 molecules DLOPQRSUeikob
#10: Protein | Mass: 34481.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#17: Protein | Mass: 24293.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#20: Protein | Mass: 23533.299 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 21345.090 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: Protein | Mass: 21568.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#23: Protein | Mass: 23516.234 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#24: Protein | Mass: 20749.391 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 14996.183 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#35: Protein | Mass: 15959.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#39: Protein | Mass: 12363.977 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#41: Protein | Mass: 8223.871 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#44: Protein | Mass: 13096.791 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#57: Protein | Mass: 26708.707 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Protein/peptide , 2 types, 2 molecules nEH
#43: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#84: Protein/peptide | Mass: 3637.369 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-40S ribosomal protein ... , 8 types, 8 molecules uxzBBCCRRJJAA
#48: Protein | Mass: 30002.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#51: Protein | Mass: 29658.920 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#52: Protein | Mass: 28751.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#59: Protein | Mass: 22168.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#60: Protein | Mass: 24263.387 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#64: Protein | Mass: 14538.987 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#79: Protein | Mass: 9480.186 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#81: Protein | Mass: 14498.884 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Small ribosomal subunit protein ... , 4 types, 4 molecules vMMHHNN
#49: Protein | Mass: 31328.543 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
---|---|
#66: Protein | Mass: 16302.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#73: Protein | Mass: 9139.337 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#76: Protein | Mass: 15463.333 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Non-polymers , 2 types, 291 molecules 


#85: Chemical | ChemComp-ZN / #86: Chemical | ChemComp-MG / |
---|
-Details
Has ligand of interest | N |
---|---|
Has protein modification | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: NAC: Ribosome nascent chain complex(Oxa1L) / Type: RIBOSOME Entity ID: #2-#4, #6-#13, #15, #18-#20, #22-#26, #28-#31, #33-#34, #36, #38-#39, #41-#43, #46-#53, #56-#84, #1 Source: MULTIPLE SOURCES |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1400 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 32 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
EM software |
| ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||
3D reconstruction | Resolution: 2.65 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 72007 / Symmetry type: POINT |