Structural assembly of the bacterial essential interactome
- Systems Biology of Infection Lab, Department of Biochemistry and Molecular Biology, Biosciences Faculty, Universitat Autònoma de Barcelona, Spain
Figures
Figure 1 with 7 supplements
Analysis of essential binary complexes predicted by AlphaFold2 (AF2).
(a) Representation of protein-protein interactions (PPIs) based on their essentiality. This study focuses on interactions between essential proteins, highlighted by a green rectangle. (b) Pipeline …
Figure 1—figure supplement 1
Correlation between the ipTM score with pDockQ of high-accuracy AlphaFold2 (AF2) protein binary complexes (ipTM>0.6).
The scatter plot includes 146 high-accuracy protein-protein interactions (PPIs), with each dot representing a specific interaction. The red line in the plot represents the average line of the …
Figure 1—figure supplement 2
Correlation between the ipTM score with pDockQ2 of high-accuracy AlphaFold2 (AF2) protein binary complexes (ipTM>0.6).
The same 146 high-accuracy protein-protein interactions (PPIs) are represented in the scatter plot. Green points represent protein binary complexes discussed in this study with pDockQ2 values …
Figure 1—figure supplement 3
AlphaFold2 (AF2) predicted interfaces colored by residue conservation.
Conservation scores were computed using VESPA and range from 0 (not conserved, cyan) to 9 (highly conserved, red). The interface residues are highlighted while the rest of the protein is set to …
Figure 1—figure supplement 4
AlphaFold2 (AF2) predicted interfaces colored by residue conservation.
Conservation scores were computed using VESPA and range from 0 (not conserved, cyan) to 9 (highly conserved, red). The interface residues are highlighted while the rest of the protein is set to …
Figure 1—figure supplement 5
AlphaFold2 (AF2) predicted interfaces colored by residue conservation.
Conservation scores were computed using VESPA and range from 0 (not conserved, cyan) to 9 (highly conserved, red). The interface residues are highlighted while the rest of the protein is set to …
Figure 1—figure supplement 6
Venn diagram representing the number of essential proteins shared among the Gram-negative species.
Figure 1—figure supplement 7
Venn diagram representing the number of essential proteins shared among the Gram-positive species.
Figure 2 with 1 supplement
Essential interactomes.
(a) Gram-negative essential interactome; (b) Gram-positive essential interactome. Nodes represent essential proteins, and edges indicate interactions between them. The color of the edges reflects …
Figure 2—figure supplement 1
AlphaFold2 (AF2) predicted interfaces discussed in this work aligned with experimentally solved structures.
Experimentally derived structures are showed in light gray and the PDB codes are highlighted.
Figure 3 with 1 supplement
Core enzymes in fatty acid (FA) synthesis.
(a) FA synthesis pathway. (b) Proposed structural rearrangements in the BirA-AccB complex. Initially, the yellow arginine-rich loop and the green loop encapsulate the substrate in BirA pocket …
Figure 3—figure supplement 1
Predicted interfaces of FabG2-AcpP2 (a) and FabI2-AcpP2 (b).
The experimentally solved FabI-AcpP structure 2FHS is aligned with the AlphaFold2 (AF2) predicted model. While these AF2 complexes show substantial structural similarity, there is a significant …
Figure 4 with 1 supplement
Common mechanism in initial steps of lipopolysaccharide (LPS) synthesis pathway.
(a) Simplified Raetz pathway. (b) Top view (left), front view (center), and magnified interface (right) of GlmU-AcpP, LpxA-AcpP, and LpxD-AcpP predicted AlphaFold2 (AF2) models. GlmU contains an …
Figure 4—figure supplement 1
Electrostatic potentials of AlphaFold2 (AF2) predicted models for the GlmU-AcpP (a), LpxA-AcpP, (b), and LpxD-AcpP (c) complexes.
In all three complexes, the ligands are primarily accommodated in non-polar binding sites, while the remaining protein structure exhibits charged potentials. The color-coded representation in the …
Figure 5
Model of Lpt bridge.
(a) Schematic representation of the Lpt complex. Initially, the LptB2FGC complex extracts the LPS from the inner membrane (IM). The LPS molecule then moves from the hydrophobic pocket of LptFG to …
Figure 6 with 1 supplement
Organization of the Sec translocon.
(a) Schematic representation of the Sec translocon and its crosstalk with the Bam translocon. During protein translocation, the preprotein engages with the central cavity of SecY, where the …
Figure 6—figure supplement 1
Sec translocon bound to SecA.
(a) Detailed view of the AlphaFold2 (AF2) model of the Sec translocon. The N-terminal helix of YidC is accommodated inside the central cavity of the Sec translocon. (b) SecE’s hinge is facing the …
Figure 7 with 1 supplement
Organization of the Lol complex.
(a) Schematic depiction of the Lol complex. The outer membrane (OM), inner membrane (IM), periplasm (P), and cytoplasm (C) are highlighted in the figure. The structures of LolA and LolB are shown in …
Figure 7—figure supplement 1
Predicted interfaces of LolA with LolC and LolE.
(a) This LolAC model displays a high level of confidence, indicating successful accommodation of the protruding β-hairpin loop within LolA. The LolAC crystal structure 6F3Z is aligned to the …
Figure 8 with 3 supplements
Divisome and elongasome predicted complexes.
The initial step of cell division involves the binding of the polymer FtsZ to inner membrane proteins FtsA. FtsEX assists in converting the polymer form of FtsA to its individual subunit form, which …
Figure 8—figure supplement 1
AlphaFold2 (AF2) model of the FtsE2X2 complex.
FtsEX is a type of ATP-binding cassette (ABC) transporter that has a role in regulating the breakdown of peptidoglycan (PG) and the divisome. FtsE is a component that binds to ATP and is found in …
Figure 8—figure supplement 2
Detailed view of AlphaFold2 (AF2) divisome model.
FtsL and FtsB proteins interact with each other, forming a coiled-coil structure. Furthermore, the C-terminal domains of FtsLB engage in an antiparallel β-sheet structure with FtsQ and FtsI …
Figure 8—figure supplement 3
Detailed view of AlphaFold2 (AF2) elongasome model.
The figure presents two views of the elongasome model: a front view on the left and a lateral view on the right. In the front view, the interface region between MrdAB and MreB is magnified. It …
Figure 9 with 1 supplement
Complexes involved in DNA replication and synthesis.
(a) Predicted interface between DNA polymerase I (PolA) and DnaN2. (b) Models of GyrAB and GyrA-FolP (top). Close-up view of the GyrA-FolP interface and comparison with the crystal structure of FolP …
Figure 9—figure supplement 1
AlphaFold2 (AF2) prediction for DnaA4 complex.
DnaA is composed of four domains: domains I, II, III, and IV. Among these, domains III (violet) and IV (green) have been more extensively studied and characterized. Domain III of DnaA is responsible …
Figure 10
Organization of the Ubi metabolon.
(a) Simplified ubiquinone synthesis pathway from 4-HB. 4-HB: 4-hydroxybenzoic acid, OPP: octaprenyl diphosphate. (b) Architecture of the Ubi metabolon. The numbers indicate the six reactions carried …
Author response image 1
Tables
Table 1
Protein complexes discussed in this work.
The ipTM score is shown along with the PDB accessions for the cases where the structure has already been solved. The AlphaFold2 (AF2) predictions are structurally aligned with the experimental …
| Protein | ipTM | PDB* | ModelArchive ID | Function |
|---|---|---|---|---|
| AccB-BirA | 0.841 | – | ma-sysbio-bei-02 | Fatty acid synthesis |
| AccABCD | 0.809 | – | ma-sysbio-bei-01 | Fatty acid synthesis |
| AcpP-FabG | 0.757 | – | ma-sysbio-bei-06 | Fatty acid synthesis |
| AcpP-FabI | 0.753 | 2FHS | ma-sysbio-bei-07 | Fatty acid synthesis |
| AcpP3-GlmU3 | 0.908 | – | ma-sysbio-bei-03 | Lipopolysaccharide synthesis |
| AcpP3-LpxA3 | 0.940 | – | ma-sysbio-bei-04 | Lipopolysaccharide synthesis |
| AcpP3-LpxD3 | 0.957 | 4IHF | ma-sysbio-bei-05 | Lipopolysaccharide synthesis |
| LptC-LptD | 0.695 | – | ma-sysbio-bei-24 | Lipopolysaccharide transport |
| LptCAD | 0.600 | – | ma-sysbio-bei-23 | Lipopolysaccharide transport |
| SecYEDF-YidC | 0.642 | 5MG3 | ma-sysbio-bei-27 | Outer membrane protein transport |
| SecYEDFA-YidC | 0.632 | – | ma-sysbio-bei-26 | Outer membrane protein transport |
| LolA-LolC | 0.809 | 6F3Z | ma-sysbio-bei-22 | Lipoprotein transport |
| LolA-LolB | 0.838 | – | ma-sysbio-bei-21 | Lipoprotein transport |
| FtsA3 | 0.761 | – | ma-sysbio-bei-13 | Cell division |
| FtsZ3 | 0.614 | – | ma-sysbio-bei-18 | Cell division |
| FtsA3-FtsZ3 | 0.542 | – | ma-sysbio-bei-14 | Cell division |
| FtsQLBWIN | 0.727 | – | ma-sysbio-bei-17 | Cell division |
| FtsQLBK | 0.572 | – | ma-sysbio-bei-16 | Cell division |
| FtsE2-FtsX2 | 0.856 | – | ma-sysbio-bei-15 | Cell division |
| MreB4CD-RodZ-MrdAB | 0.764 | – | ma-sysbio-bei-12 | Cell division |
| DnaA4 | 0.545 | – | ma-sysbio-bei-08 | DNA replication |
| DnaN-PolA | 0.813 | – | ma-sysbio-bei-11 | DNA replication |
| DnaB-DnaI | 0.750 | – | ma-sysbio-bei-10 | DNA replication |
| DnaB-DnaC | 0.650 | 6KZA | ma-sysbio-bei-09 | DNA replication |
| NrdE-NrdF | 0.856 | – | ma-sysbio-bei-25 | DNA replication |
| GyrA-GyrB | 0.715 | 6RKU | ma-sysbio-bei-20 | DNA replication |
| GyrA-FolP | 0.847 | – | ma-sysbio-bei-19 | DNA replication |
| UbiEFGHIJK | 0.806 | – | ma-sysbio-bei-28 | Ubiquinone synthesis |
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*
Complexes FtsA3-FtsZ3 and FtsQLBK have an ipTM score <0.6 because they contain large intrinsically disordered segments that, despite not participating in the interaction, contribute to decrease the global ipTM score.
Author response table 1
Performance of state-of-the-art PPI prediction methods (Huang et al., 2023).
| Methods | AUPRC* |
|---|---|
| SGPPI | 0.422 |
| Profppikernel | 0.359 |
| PIPR | 0.342 |
| PIPE2 | 0.220 |
| SigProd | 0.264 |
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*
AUPRC denotes the average AUPRC value of 10-fold cross-validation.
Additional files
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Supplementary file 1
List of validated bacterial complexes.
The listed complexes were not included in the training dataset of AF and share <30% sequence identity with all models deposited in the PDB.
- https://cdn.elifesciences.org/articles/94919/elife-94919-supp1-v2.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/94919/elife-94919-mdarchecklist1-v2.pdf
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Source data 1
Essential protein annotations and protein-protein interactions (PPIs) scores provided by AlphaFold2 (AF2).
- https://cdn.elifesciences.org/articles/94919/elife-94919-data1-v2.xlsx
