8K82 image
Deposition Date 2023-07-28
Release Date 2024-07-10
Last Version Date 2024-11-06
Entry Detail
PDB ID:
8K82
Keywords:
Title:
Cryo-EM structure of the yeast 80S ribosome with tigecycline, Not5 and P-site tRNA
Biological Source:
Source Organism(s):
Method Details:
Experimental Method:
Resolution:
3.00 Å
Aggregation State:
PARTICLE
Reconstruction Method:
SINGLE PARTICLE
Macromolecular Entities
Polymer Type:polyribonucleotide
Molecule:23S rRNA
Chain IDs:D (auth: C1)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polyribonucleotide
Molecule:18S rRNA
Chain IDs:A (auth: C2)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polyribonucleotide
Molecule:5.8S rRNA
Chain IDs:F (auth: C3)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polyribonucleotide
Molecule:5S rRNA
Chain IDs:E (auth: C4)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polyribonucleotide
Molecule:tRNA
Chain IDs:C (auth: C5)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polyribonucleotide
Molecule:mRNA
Chain IDs:B (auth: C7)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:General negative regulator of
Gene (Uniprot):NOT5
Chain IDs:GC (auth: CN)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL1A
Chain IDs:EC (auth: L1)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL2A
Chain IDs:NA (auth: LA)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL3
Chain IDs:OA (auth: LB)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL4A
Chain IDs:PA (auth: LC)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL5
Chain IDs:QA (auth: LD)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL6A
Chain IDs:RA (auth: LE)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL7A
Chain IDs:SA (auth: LF)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL8A
Chain IDs:TA (auth: LG)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL9A
Chain IDs:UA (auth: LH)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL10
Chain IDs:VA (auth: LI)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL11A
Chain IDs:WA (auth: LJ)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL12A
Chain IDs:XA (auth: LK)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL13A
Chain IDs:YA (auth: LL)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL14A
Chain IDs:ZA (auth: LM)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL15A
Chain IDs:AB (auth: LN)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL16A
Chain IDs:BB (auth: LO)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL17A
Chain IDs:CB (auth: LP)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL18A
Chain IDs:DB (auth: LQ)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL19A
Chain IDs:EB (auth: LR)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL20A
Chain IDs:FB (auth: LS)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL21A
Chain IDs:GB (auth: LT)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL22A
Chain IDs:HB (auth: LU)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL23A
Chain IDs:IB (auth: LV)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL24A
Chain IDs:JB (auth: LW)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL25
Chain IDs:KB (auth: LX)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL26A
Chain IDs:LB (auth: LY)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL27A
Chain IDs:MB (auth: LZ)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL28
Chain IDs:NB (auth: La)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL29
Chain IDs:OB (auth: Lb)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL30
Chain IDs:PB (auth: Lc)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL31A
Chain IDs:QB (auth: Ld)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL32
Chain IDs:RB (auth: Le)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL33A
Chain IDs:SB (auth: Lf)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL34A
Chain IDs:TB (auth: Lg)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL35A
Chain IDs:UB (auth: Lh)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL36A
Chain IDs:VB (auth: Li)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL37A
Chain IDs:WB (auth: Lj)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL38
Chain IDs:XB (auth: Lk)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL39
Chain IDs:YB (auth: Ll)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Ubiquitin-ribosomal protein e
Gene (Uniprot):RPL40A
Chain IDs:ZB (auth: Lm)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL41A
Chain IDs:AC (auth: Ln), BC (auth: L2)
Chain Length:0
Number of Molecules:2
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL42A
Chain IDs:CC (auth: Lo)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPL43A
Chain IDs:DC (auth: Lp)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):RPP0
Chain IDs:FC (auth: P0)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS0A
Chain IDs:G (auth: SA)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S1-A
Gene (Uniprot):RPS1A
Chain IDs:H (auth: SB)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S2
Gene (Uniprot):RPS2
Chain IDs:I (auth: SC)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS3
Chain IDs:J (auth: SD)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S4-A
Gene (Uniprot):RPS4A
Chain IDs:K (auth: SE)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS5
Chain IDs:L (auth: SF)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S6-A
Gene (Uniprot):RPS6A
Chain IDs:M (auth: SG)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S7-A
Gene (Uniprot):RPS7A
Chain IDs:N (auth: SH)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S8-A
Gene (Uniprot):RPS8A
Chain IDs:O (auth: SI)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S9-A
Gene (Uniprot):RPS9A
Chain IDs:P (auth: SJ)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS10A
Chain IDs:Q (auth: SK)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS11A
Chain IDs:R (auth: SL)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS12
Chain IDs:S (auth: SM)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S13
Gene (Uniprot):RPS13
Chain IDs:T (auth: SN)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S14-A
Gene (Uniprot):RPS14A
Chain IDs:U (auth: SO)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS15
Chain IDs:V (auth: SP)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS16A
Chain IDs:W (auth: SQ)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS17A
Chain IDs:X (auth: SR)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS18A
Chain IDs:Y (auth: SS)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS19A
Chain IDs:Z (auth: ST)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS20
Chain IDs:AA (auth: SU)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS21A
Chain IDs:BA (auth: SV)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S22-A
Gene (Uniprot):RPS22A
Chain IDs:CA (auth: SW)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S23-A
Gene (Uniprot):RPS23A
Chain IDs:DA (auth: SX)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S24-A
Gene (Uniprot):RPS24A
Chain IDs:EA (auth: SY)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS25A
Chain IDs:FA (auth: SZ)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS26B
Chain IDs:GA (auth: Sa)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S27-A
Gene (Uniprot):RPS27A
Chain IDs:HA (auth: Sb)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS28A
Chain IDs:IA (auth: Sc)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):RPS29A
Chain IDs:JA (auth: Sd)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:40S ribosomal protein S30-A
Gene (Uniprot):RPS30A
Chain IDs:KA (auth: Se)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Ubiquitin-ribosomal protein e
Gene (Uniprot):RPS31
Chain IDs:LA (auth: Sf)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):ASC1
Chain IDs:MA (auth: Sg)
Chain Length:0
Number of Molecules:1
Biological Source:Saccharomyces cerevisiae
Primary Citation
Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.
Nat Commun 15 5481 5481 (2024)
PMID: 38942792 DOI: 10.1038/s41467-024-49797-7

Abstact

Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.

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Primary Citation of related structures
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