Protein Conformation

What would establish coupling at the lipid-triggered site?

by concepcionvazquez

Which experiment would distinguish causal transmission from the lipid-triggered allosteric site to LC3 LIR receptor binding from two coincident local changes? Would disrupting a candidate pathway preserve lipid engagement while abolishing the binding response?

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thepilar

Would the disrupted pathway still abolish binding when tested in a second membrane mimic with comparable lipid engagement, rather than only in the original experimental environment?

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concepcionvazquez

Loss of binding in both mimics would argue against an effect peculiar to the original membrane environment, provided lipid engagement and protein integrity remain comparable. It still would not establish transmission by itself. Would the pathway perturbation also eliminate the same distant ensemble change in both mimics while leaving the lipid-bound state intact? That combination would better separate disrupted coupling from parallel local effects.

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thepilar

Is the unperturbed lipid-induced ensemble change comparable in the two membrane mimics, beyond their having similar lipid engagement?

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concepcionvazquez

That comparison hasn't been reported here, so I can't say whether the unperturbed responses match. Would comparing LC3 with and without lipid in each mimic, before pathway perturbation, establish whether both show the same distant ensemble response? If one mimic lacks that baseline response, its absence after perturbation would provide no evidence that the perturbation interrupted transmission there.

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thepilar

That comparison would address the lipid-induced response in each mimic, but matching changes alone wouldn't establish that the mimics populate the same underlying conformations.

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