Table 1.

Residues of the mTSPO/PK11195 complex located either in the protein binding cavities or at the dimer interface, according to the experimental data [20] and to the proposed dimer models. These models are based either on the NMR structure (mTSPO_NMR, [20] and this work) or on the protein from Rhodobacter Sphaeroides (RsTSPO, this work). Residues at the interface accordingly to both the NMR data [20] and mTSPO_Rs are in bold. mTSPO_Rs’ binding pockets do not include exactly the same residues because of differences of the ligands’ binding poses, as obtained with docking simulations described in the text. On the contrary, mTSPO_NMR binding pockets include by construction exactly the same residues. The residues within 5 Å from the ligand are assigned to the binding cavity and reported in this table. The corresponding list of the residues within 4 Å and 6 Å from the ligand is shown in Table S6 and Figure S5. We report also a list of the residues with a conservation rate higher than 85% in multiple sequence alignment across 148 homologous sequences to the mTSPO, as determined with the ConSurf server [33], along with the topological area of the protein where these sequences are found. A detailed discussion of the evolutionary coupling of the residues is presented in the Results section and in Figure S6.

Region	Inferred by Experiment	mTSPO_NMR		mTSPO_Rs
Binding Cavity	G19, A23, V26, R27, H43, R46, L49, A50, I52, W53, W95, W107, A110, D111, L114, W143, A147, L150, N151	Subunit A	Subunit B	Subunit A	Subunit B
		G18, G19, F20, G22, A23, V26, R27, G30, L31, K39, P40, S41, H43, P44, P45, R46, L49, A50, I52, W53, W93, W95, W107, A108, A110, D111, L114, W143, F146, A147, T148, L150, N151	G18, G19, F20, G22, A23, V26, R27, G30, L31, K39, P40, S41, H43, P44, P45, R46, L49, A50, I52, W53, W93, W95, W107, A108, A110, D111, L114, W143, F146, A147, T148, L150, N151	P15, G18, G19, M21, G22, A23, F25, V26, R27, G28, E29, Y34, K39, H43, P44, R46, L49, A50, W53, G54, Y57, N92, W93, W95, P96, F99, F100, L112, W143, F146, A147, T148, L150, N151, V154	G18, M21, G22, A23, F25, Y34, H43, P44, R46, L49, A50, W53, L56, Y57, N92, W93, A9, W95, P96, P97, F99, F100, L112, V115, Y140, L141, W143, A147, L150
Dimer Interface	V80, G83, Q88, N92, W93, W95, I98, F100, G101, A102, D111, V118	F74, T75, E76, D77, M79, V80, P81, G83, L84, T86, G87, Q88, A90, L91		V6, P7, G10, L11, L13, V14, L17, G18, F20, M21, Y24 V26, R27(A) M79, V80, L82, G83, L84, Y85, T86, G87, A90, L91, W93, A94, P97, I98, A102, Q104, W107, A108, A110, D111, L114, V118, A121, A125
Conserved Residues	LP-I: L37, P40, P44, P45, TM-II: W53, L56, G61, TM-III: N92, W95, F99, F100, TM-V: L136, P139, Y140, W143, A147, L150, N151
Evolutionary Coupling	P40, P45 coevolve with L150; P44, P45 with W95; W53 with L56, A147, L150; W95 with A147 and N151