Hi there,
As part of my dissertation, I am trying to understand how the open/closed conformational changes of the RBD contribute to SARS-CoV-2 binding to neuropilin-1. My main question is if furin cleavage of the S1/S2 site occurs prior to the possible open/close conformations forming.
Any help would be greatly appreciated!
There's a good paper in nature structural and molecular biology that Addresses this, Xiong et al. In brief, the protease acts on the closed or profusion conformation allowing the timer to transition to an open formation that exposes the rbd so that it can bind and catalyze fusion with the host cell membrane. I am not sure how this specifally relates to neuropilin 1 binding however, you will need to compare structures to confirm that the rbd are the same for ace2 and neuropilin1
Hello, Benn!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457603/
Article Furin cleavage of the SARS coronavirus spike glycoprotein en...
The insertion of a furin cleavage site (PRRA) upstream of the S1 cleavage site distinguishes SARS-CoV-2. Based on the SARS-CoV S protein structure, the insertion occurs in an exterior loop of the SARS-CoV-2 spike below the spike globular head and away from the receptor binding domain (Fig. 1B)
Hi Ben,
Please see this paper by Shang et al.
https://www.pnas.org/content/117/21/11727
They suggest that furin cleavage is a preactivation event during the endocytic pathway to compensate for the mostly lying down position of the RBD. Hence it should be called an upstream event to RBD binding (in standing up position).
The conformational change does make it vulnerable to the furin change, however, it works by stages. Itis easier by stages, butthe S protein does have its own mechanisms to dodge the attacks. You might still stop the S protein but it will certainly be harder.
I wish I can suport it with references. If I can I will write again.