Table 1.
Crystal structures of BAK: observations on the 7D10 epitope and residue M60.
| -----------------Contacts----------------- | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PDB | Space group | Unit cell edge (Å) | Resoln (Å) | N | M/D | ligand | (i) P55 | (ii) D57 | (iii) E59 | (iv) M60 | ||
| 2IMS | C2 | 57.5 | 53.7 | 58.3 | 1.48 | 1 | M | apo | + | + | + | + |
| 2IMT | C2 | 57.3 | 53.6 | 58.1 | 1.49 | 1 | M | apo | + | + | + | + |
| 2JCN | P6522 | 62.8 | 62.8 | 138.1 | 1.8 | 1 | M | apo | + | + | + | + |
| 2YV6 | P6522 | 61.8 | 61.9 | 137.5 | 2.5 | 1 | M | apo | + | + | + | + |
| 4U2U | C2 | 110.6 | 39.5 | 88.1 | 2.9 | 2 | D | apo | − | − | − | − |
| 5VWV | P4132 | 139.4 | 1.9 | 1 | D | BIMa | + | + | + | + | ||
| 5VWW | P43212 | 87.8 | 87.8 | 95.5 | 2.8 | 2 | D | BIMa | − | − | − | − |
| 5VWX | P212121 | 61.6 | 76.5 | 77.5 | 2.5 | 2 | D | BIMb | − | − | − | − |
| 5VWY | C2 | 65.9 | 37.5 | 69.6 | 1.56 | 1 | D | BIMc | − | + | + | + |
| 5VWZ | P21 | 38.2 | 56.7 | 79.3 | 1.62 | 2 | M | BIMd | − | + | + | + |
| 5VX0 | P212121 | 48.1 | 63.2 | 121.0 | 1.6 | 2 | M | BIMe | − | + | + | + |
| 5VX1 (hsBAK L100A) | P21 | 41.5 | 39.5 | 108.1 | 1.22 | 2 | M | apo | − | − | − | + |
| 6MCY (mmBAK) | P1 | 37.0 | 59.3 | 79.2 | 1.75 | 4 | M | apo | + | + | + | + |
N: number of BAK molecules in the asymmetric unit.
M/D: monomer/dimer; all dimers here are core/latch dimers resulting from pre-treatment of BAK with CHAPS and BID BH3
BIM: five different BH3 ligands, see details in Brouwer et al. [16].
Contacts: (i) P55-L140 (ii) D57-Y143 (iii) E59-backbone NH of 149 and 150 (iv) M60 in pocket formed from residues in α1, α5 and α6.
In some cases (4U2U, 5VWW, 5VWX, 5VWY), absence of an interaction (−) is due to epitope disorder in that crystal structure.
In an NMR structure of BAK bound to a stapled peptide (PDB code 2MB5) the loop between helices 1 and 2 (including M60) is disordered.
Several conformational changes accompany the L100A mutation [16]. Helix α3 is extended by two residues (H99 and A100) and the helix is shifted towards its N-terminus by ~1.5 Å, the α3-α4 loop is altered, helix α4 starts at residue A107 (not A104 as for wild-type), the α2-α3 connection is less helical and the C-terminus of helix α1 and the 7D10 epitope is altered.