Title : An unexpected N-terminal loop in
PD-1 dominates binding by nivolumab
Abstract :
- Cancer immunotherapy by targeting of immune checkpoint molecules has been a research 'hot-spot' in recent years
- Nivolumab, a human monoclonal antibody targeting PD-1 , has been widely used clinically since 2014
- However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/ PD-1
- It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition
- Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab
- Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1
- This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all
- Nivolumab binds to a completely different area than pembrolizumab
- These results provide the basis for the design of future inhibitory molecules targeting PD-1
Output (sent_index, trigger,
protein,
sugar,
site):
- 3. pembrolizumab/PD-1, , PD-1, the complex structure, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):