Neuron-Like Networks Between Ribosomal Proteins Within the Ribosome

From brain to the World Wide Web, information-processing networks share common scale invariant properties. Here, we reveal the existence of neural-like networks at a molecular scale within the ribosome. We show that with their extensions, ribosomal proteins form complex assortative interaction networks through which they communicate through tiny interfaces. The analysis of the crystal structures of 50S eubacterial particles reveals that most of these interfaces involve key phylogenetically conserved residues. The systematic observation of interactions between basic and aromatic amino acids at the interfaces and along the extension provides new structural insights that may contribute to decipher the molecular mechanisms of signal transmission within or between the ribosomal proteins. Similar to neurons interacting through “molecular synapses”, ribosomal proteins form a network that suggest an analogy with a simple molecular brain in which the “sensory-proteins” innervate the functional ribosomal sites, while the “inter-proteins” interconnect them into circuits suitable to process the information flow that circulates during protein synthesis. It is likely that these circuits have evolved to coordinate both the complex macromolecular motions and the binding of the multiple factors during translation. This opens new perspectives on nanoscale information transfer and processing.


Table S1
Properties of the extensions of the eukaryotic ribosomes (from the pdb structure 4v88)  Helix Length (aas) β-HP size 50S eubact.

Table S3
List of the intermolecular interactions between the ribosomal proteins within the 60S subunit of the eukaryotic ribosome (from the pdb structure 4v88). Colour code: light pink: 3 extensions; light blue: 2 extensions; light green: 1 extension; white: without extension.

Table S4
List of the intermolecular interactions between the ribosomal proteins within the 40S subunit of the eukaryotic ribosome (from the pdb structure 4v88). Colour code as in Table S3.

Table S5
List of the intermolecular interactions between the ribosomal proteins within the 50S subunit of the archaeal ribosome (from the pdb structure 1s72). Colour code as in Table S3.

Table S6
List of the intermolecular interactions between the ribosomal proteins within the 50S subunit of the eubacterial ribosome (from the pdb structure 4v8i). Colour code as in Table S3.

Table S7
List of the intermolecular interactions between the ribosomal proteins within the 30S subunit of the eubacterial ribosome (from the pdb structure 4v8i). Colour code as in Table S3.

Table S12
Conserved residues at the interfaces of the interacting proteins within the 50S eubacterial subunit. Left column: residues found in the interface. Right column: conserved interface residues. Residues whose properties conserved are underlined and strictly conserved residues are written in bold. AR: conserved aromatic residues; BA: conserved basic residues; AC: conserved acid residues; HP: conserved hydrophobic residues; PO: conserved polar residues; SM: conserved small chain residues. See also figure uS5 that displays the consensus sequence from sequence alignments (reference 6 in Methods).

Table S15
Status of the pdb models when different conformations are observed at protein-protein interfaces of 50S subunits and 70S eubacterial ribosomes.
For each protein-pairs where different conformations have been observed, the status of the models is noted as follow: white: correct model; "?" and green: the map is not incompatible with the different model built in the map; "-" and yellow: non-interpretable electron density map in the corresponding region; "x" and red: incorrect model, the model is not correctly fitted into its density map. For uL16-bL27, the "S" indicates that bL27 is fully structured at the interface (see also Supplementary fig. S10
The arrows indicate the residues in contact with another protein.   Figure S10: Correct and incorrect (x) models at the protein-protein interfaces of 50S and 70S pdb structures listed in table S15. Our careful inspection of electron density maps of each structure has revealed that except ul15-bL21 (that has been marked "?" in table S15), most of the models "x" are probably the results of a misinterpretation of a not well-resolved electron density map in the region.
10. bL20 -uL4 uL4 uL4 bL20 bL20  Figure S11: Comparison of the electron density maps of the alternative models at the protein-protein interfaces reported in table S15. Left: correct models; right: incorrect (x) models.

Correct
Incorrect ( right: alternative model "?" observed in the second molecule of the asymmetric unit of 4v8b. The two aromatic residues of bL21 phe 75 and tyr 81 are on the same side of the b-sheet. This alternative structure is compatible with the corresponding electron density map. However this structure only observed in a set of pdb entry marked "?" in table S15. e: uL33-bL35 interface in the T. thermophilus 70S ribosome left: correct model found in the 2.5 Å resolution 4y4p structure right: incorrect model found in the molecule 2 of 4v6f structure. His 31 has been fitted into a peak that correspond to a Mg 2+ ion in the high resolution structure. f: uL15-bL35 interface in the T. thermophilus 70S ribosome (continued) left: correct model found in the molecule 1 of 4v6f and other high-resolution structures of the T. thermophilus 70S ribosome. right: incorrect model found in the molecule 2 of the 4v6f structure. Lys 47 has been fitted into the density peak of phe 48 that becomes extruded out of density.

bL35-bL33
Correct Incorrect (x) f Figure S11 (continued) g: bL17-bL32 interface in the T. thermophilus 70S ribosome left: correct model found in 4v8i right: incorrect model found in the structure of 4v6f. The tyrosines 51 and 52 of bL32 have been incorrectly fitted due to an interpretable map in this region.
h: bL17-uL3 interface in the T. thermophilus 70S ribosome left: correct model found in 4v8i and other high-resolution structures of the T. thermophilus 70S ribosome. right: incorrect model found in the structure of 4v9h. His 3 and leu 4 of bL17 have been incorrectly fitted due to an interpretable map in this region.

Correct
Incorrect (x)