7NHN

VgaL, an antibiotic resistance ABCF, in complex with 70S ribosome from Listeria monocytogenes


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens.

Crowe-McAuliffe, C.Murina, V.Turnbull, K.J.Kasari, M.Mohamad, M.Polte, C.Takada, H.Vaitkevicius, K.Johansson, J.Ignatova, Z.Atkinson, G.C.O'Neill, A.J.Hauryliuk, V.Wilson, D.N.

(2021) Nat Commun 12: 3577-3577

  • DOI: https://doi.org/10.1038/s41467-021-23753-1
  • Primary Citation of Related Structures:  
    7NHK, 7NHL, 7NHM, 7NHN

  • PubMed Abstract: 

    Target protection proteins confer resistance to the host organism by directly binding to the antibiotic target. One class of such proteins are the antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F-subtype (ARE-ABCFs), which are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition from antibiotics that target the large ribosomal subunit. Here, we present single-particle cryo-EM structures of ARE-ABCF-ribosome complexes from three Gram-positive pathogens: Enterococcus faecalis LsaA, Staphylococcus haemolyticus VgaA LC and Listeria monocytogenes VgaL. Supported by extensive mutagenesis analysis, these structures enable a general model for antibiotic resistance mediated by these ARE-ABCFs to be proposed. In this model, ABCF binding to the antibiotic-stalled ribosome mediates antibiotic release via mechanistically diverse long-range conformational relays that converge on a few conserved ribosomal RNA nucleotides located at the peptidyltransferase center. These insights are important for the future development of antibiotics that overcome such target protection resistance mechanisms.


  • Organizational Affiliation

    Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lmo0919 proteinA [auth 0]567Listeria monocytogenes EGD-eMutation(s): 2 
Gene Names: lmo0919
UniProt
Find proteins for Q8Y8I3 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L2F [auth G]277Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P60426 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3G [auth H]209Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L4H [auth I]207Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P61055 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L5I [auth J]179Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L6J [auth K]178Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L13K [auth M]145Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 12
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L14L [auth N]122Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 13
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L15M [auth O]146Listeria monocytogenes EGD-eMutation(s): 0 
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Entity ID: 14
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L16N [auth P]144Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 15
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L17O [auth Q]135Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 16
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L18P [auth R]119Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 17
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L19Q [auth S]114Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for O53083 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 18
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L20R [auth T]119Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 19
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L21S [auth U]102Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 20
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L22T [auth V]118Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for Q927L2 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 21
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L23U [auth W]94Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 22
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L24V [auth X]103Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 23
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L27W [auth Z]96Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P66125 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 24
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L28X [auth 1]62Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 25
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L29Y [auth 2]63Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 26
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L30Z [auth 3]59Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 27
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L32-2AA [auth 5]57Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P66207 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 28
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L33 1BA [auth 6]49Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 29
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L34CA [auth 7]44Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 30
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L35DA [auth 8]66Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 31
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L36EA [auth 9]37Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 33
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S2GA [auth c]249Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for Q8Y6M6 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 34
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S3HA [auth d]218Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 35
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S4IA [auth e]200Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 36
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S5JA [auth f]167Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 37
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S6KA [auth g]97Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 38
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S7LA [auth h]156Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 39
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S8MA [auth i]132Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 40
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S9NA [auth j]130Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 41
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S10OA [auth k]102Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 42
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S11PA [auth l]129Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 43
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S12QA [auth m]137Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 44
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S13RA [auth n]121Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 45
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S14 type ZSA [auth o]61Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
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Entity ID: 46
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S15TA [auth p]89Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for Q92C24 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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UniProt GroupQ92C24
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Entity ID: 47
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S16UA [auth q]90Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for Q8Y699 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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UniProt GroupQ8Y699
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Entity ID: 48
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S17VA [auth r]87Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for Q927L6 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 49
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S18WA [auth s]79Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P66461 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 50
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S19XA [auth t]92Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P66484 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 51
MoleculeChains Sequence LengthOrganismDetailsImage
30S ribosomal protein S20YA [auth u]84Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P66503 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 52
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L31 type BZA [auth 4]81Listeria monocytogenes EGD-eMutation(s): 0 
UniProt
Find proteins for P0A485 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
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Entity ID: 2
MoleculeChains LengthOrganismImage
tRNA-fMetB [auth D]77Listeria monocytogenes EGD-e
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Entity ID: 3
MoleculeChains LengthOrganismImage
RNA (5'-R(P*GP*AP*GP*GP*UP*NP*NP*NP*NP*NP*NP*AP*UP*G)-3')C [auth b]14Listeria monocytogenes EGD-e
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Entity ID: 4
MoleculeChains LengthOrganismImage
23S rRNAD [auth A]2,928Listeria monocytogenes EGD-e
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Entity ID: 5
MoleculeChains LengthOrganismImage
16S rRNAE [auth a]1,542Listeria monocytogenes EGD-e
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Entity ID: 32
MoleculeChains LengthOrganismImage
5S rRNAFA [auth B]114Listeria monocytogenes EGD-e
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Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
AB [auth 0],
BB [auth 0]
ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
SPD
Query on SPD

Download Ideal Coordinates CCD File 
GB [auth A],
IG [auth a]
SPERMIDINE
C7 H19 N3
ATHGHQPFGPMSJY-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
LH [auth 5],
MH [auth 9],
OH [auth o]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
K
Query on K

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EC [auth A]
GD [auth A]
JC [auth A]
JE [auth A]
KC [auth A]
EC [auth A],
GD [auth A],
JC [auth A],
JE [auth A],
KC [auth A],
KH [auth P],
LD [auth A],
NC [auth A],
OC [auth A],
OE [auth A],
OG [auth a],
PE [auth A],
PF [auth A],
SF [auth A],
TE [auth A],
TF [auth A],
TG [auth a],
UD [auth A],
WG [auth a],
YC [auth A],
ZE [auth A]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
AC [auth A]
AD [auth A]
AE [auth A]
AF [auth A]
AG [auth A]
AC [auth A],
AD [auth A],
AE [auth A],
AF [auth A],
AG [auth A],
AH [auth a],
BC [auth A],
BD [auth A],
BE [auth A],
BF [auth A],
BG [auth A],
BH [auth a],
CB [auth 0],
CC [auth A],
CD [auth A],
CE [auth A],
CF [auth A],
CG [auth A],
CH [auth a],
DB [auth 0],
DC [auth A],
DD [auth A],
DE [auth A],
DF [auth A],
DG [auth A],
DH [auth a],
EB [auth D],
ED [auth A],
EE [auth A],
EF [auth A],
EG [auth A],
EH [auth a],
FB [auth b],
FC [auth A],
FD [auth A],
FE [auth A],
FF [auth A],
FG [auth A],
FH [auth a],
GC [auth A],
GE [auth A],
GF [auth A],
GG [auth A],
GH [auth a],
HB [auth A],
HC [auth A],
HD [auth A],
HE [auth A],
HF [auth A],
HG [auth A],
HH [auth G],
IB [auth A],
IC [auth A],
ID [auth A],
IE [auth A],
IF [auth A],
IH [auth H],
JB [auth A],
JD [auth A],
JF [auth A],
JG [auth a],
JH [auth O],
KB [auth A],
KD [auth A],
KE [auth A],
KF [auth A],
KG [auth a],
LB [auth A],
LC [auth A],
LE [auth A],
LF [auth A],
LG [auth a],
MB [auth A],
MC [auth A],
MD [auth A],
ME [auth A],
MF [auth A],
MG [auth a],
NB [auth A],
ND [auth A],
NE [auth A],
NF [auth A],
NG [auth a],
NH [auth o],
OB [auth A],
OD [auth A],
OF [auth A],
PB [auth A],
PC [auth A],
PD [auth A],
PG [auth a],
QB [auth A],
QC [auth A],
QD [auth A],
QE [auth A],
QF [auth A],
QG [auth a],
RB [auth A],
RC [auth A],
RD [auth A],
RE [auth A],
RF [auth A],
RG [auth a],
SB [auth A],
SC [auth A],
SD [auth A],
SE [auth A],
SG [auth a],
TB [auth A],
TC [auth A],
TD [auth A],
UB [auth A],
UC [auth A],
UE [auth A],
UF [auth A],
UG [auth a],
VB [auth A],
VC [auth A],
VD [auth A],
VE [auth A],
VF [auth A],
VG [auth a],
WB [auth A],
WC [auth A],
WD [auth A],
WE [auth A],
WF [auth A],
XB [auth A],
XC [auth A],
XD [auth A],
XE [auth A],
XF [auth A],
XG [auth a],
YB [auth A],
YD [auth A],
YE [auth A],
YF [auth A],
YG [auth a],
ZB [auth A],
ZC [auth A],
ZD [auth A],
ZF [auth A],
ZG [auth a]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research Foundation (DFG)GermanyWI3285/8-1
Swedish Research CouncilSweden2017-03783
Swedish Research CouncilSweden2019-01085
European Regional Development FundSweden2014-2020.4.01.15-0013
Estonian Research CouncilEstoniaPRG335
Swedish Research CouncilSweden2018-00956

Revision History  (Full details and data files)

  • Version 1.0: 2021-05-05
    Type: Initial release
  • Version 1.1: 2021-06-23
    Changes: Database references
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references