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Approaching the 5-HT3 Receptor heterogeneity by computational studies of their transmembrane and intracellular domains

Marta Del Cadia, Francesca De Rienzo, Maria Cristina Menziani*

Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy.

* Corresponding Authors:

Maria Cristina Menziani e-mail:

Table 1S- Technical checks used to select the models of the five 5-HT3R subunits: DOPE, or Discrete Optimized Protein Energy, the objective function from MODELLER,38 is a statistical potential used to asses homology models in protein structure prediction; Ramachandran values, from the software PROCHECK,42 indicate the percentage (%) or the number of residues with favourable, generously allowed and disallowed φ/ψ geometry; the G-factor evaluates the overall geometry (such as bond distances, angles…) of the protein structure and this score should be above -0.5 for a reliable model;42 the WHAT_CHECK44,45 packing quality evaluates the packing environment of the protein residues in comparison with the average packing environment for all residues of the same type in good PDB files (Z-score positive is better than the average); the overall quality factor from ERRAT43 express the percentage of the protein for which the calculated error value falls below the 95% rejection limit.

In the table are reported values obtained for the template Tm nAChR A (PDB 2BG9) and for the 5-HT3R models, which appear to be good as putative candidate, after a first visual inspection. The other 5-HT3R models were not evaluated because of their evident problems in structure. The selected model of each subunit is highlighted in italic.

Model / DOPE score / PROCHECK:
RAMACHANDRAN PLOT / WHAT_CHECK / ERRAT
Most favoured regions (%) / Generously allowed regions
(n. res.) / Disallowed regions
(n. res.) / G-factor / Z-scores: packing quality / Overall
quality factor (%)
Tm nAChR A / 89.8 / 2 / 0 / -0.16 / -2.346 / 88.96
5-HT3 subunit A / 4 / 6894 / 97.2 / 0 / 0 / 0.03 / 0.156 / 90.06
7 / 7244 / 95.8 / 0 / 0 / 0.02 / -0.040 / 86.75
8 / 7263 / 97.9 / 0 / 0 / 0.00 / -0.246 / 88.74
11 / 7057 / 96.5 / 0 / 0 / -0.08 / -0.667 / 94.70
13 / 7217 / 97.2 / 1 / 0 / 0.05 / -0.321 / 84.10
18 / 6900 / 96.5 / 0 / 0 / 0.00 / -0.297 / 83.44
19 / 6902 / 95.1 / 0 / 0 / 0.00 / -0.209 / 80.79
5-HT3 subunit B / 6 / 570.9 / 97.9 / 0 / 0 / 0.00 / -0.643 / 87.41
7 / 424.9 / 97.2 / 0 / 0 / 0.07 / -0.369 / 88.74
8 / 441.05 / 96.5 / 0 / 0 / 0.06 / -0.114 / 82.78
5-HT3 subunit C / 2 / 470 / 95.3 / 0 / 0 / -0.02 / -1.159 / 92.3
8 / 484 / 97.6 / 0 / 0 / 0.00 / -1.158 / 95.4
10 / 511 / 98.4 / 0 / 0 / -0.02 / -0.746 / 94.6
5-HT3 subunit D / 1 / 507 / 94.5 / 0 / 0 / 0.05 / -0.327 / 83.11
5 / 554 / 94.5 / 0 / 1 / -0.01 / -0.768 / 84.9
9 / 990 / 93.2 / 2 / 0 / -0.20 / -0.472 / 82.6
5-HT3 subunit E / 4 / 461 / 98.5 / 0 / 0 / 0.07 / -0.127 / 86.4
5 / 409 / 97.7 / 0 / 0 / 0.07 / 0.300 / 87.1
7 / 427 / 98.5 / 0 / 0 / 0.06 / -0.197 / 95.7
9 / 479 / 98.5 / 0 / 0 / 0.08 / -0.321 / 97.8

Figure 1S- Electrostatic properties of the homomeric 5-HT3A and 5-HT3B receptors. A slab in the direction of the pore z axis allows a view in the interior of the pore. MEPs isocontour levels are shown at +1 kT/e (blue) and −1 kT/e (red).