Figure 4 | Scientific Reports

Figure 4

From: The CC′ loop of IgV domains of the immune checkpoint receptors, plays a key role in receptor:ligand affinity modulation

Figure 4

Unusual conformation of CC′ loop leads to non-canonical IgV domain: Panel a illustrates the peeling of CC′ loop (ribbon, dark blue) of CD22 (ribbon, yellow) and CC′ loop (ribbon, Slate) of mTIM-3 in comparison with the canonical CC′ loop of hPD-1 (ribbon, cyan), from the core to form a cleft between FG loop and CC′ loop. This non-canonical conformation of CC′ loops of CD22 and mTIM-3 creates a cleft between the CC′ and FG loops (CD22 (ribbon, red) and mTIM-3 (ribbon, salmon)). Panel b illustrates the non-canonical conformation of CC′ loop (slate) which is stabilised by two non-canonical disulphide linkages (shown in sticks) in mTIM-3. Panel c illustrates the gating of the above-mentioned pocket in mTIM-3 by W41, where W41 on the CC′ loop assumes a closed conformation (stick and surface, cyan) and is present close to FG loop. W41 is flung away from FG loop to assume an open conformation (stick and surface, dark blue) to allow the entry of PtdSer. Panel d illustrates the pocket formed by CC′ loop (dark blue) and FG loop (red) of CD22, with bound α2-6 siallylactose (sticks, green). The resdiues responsible for this non-canonical CC′ loop conformation is shown in sticks (yellow).

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