What a fantastic lecture. The one I attended at university only managed to confuse me immensely, but now viral membrane fusion is much clearer to me. Thank you so much!
Great presentation -- good cartoons & charts. No-one can tell me that RNA isn't alive! Virus has to be the master of conformational change. Never realized that ATP and GTP never found outside of the cell (like maybe the ECM). Have to watch your video 'couple more times and research details. Thanks, good lookin out.
Very interesting. What are the major differences between these hemagglutinin receptors and the tSNARE and vSNARE receptors used during exocytosis of neurotransmitters?
Nice question..Here's what I know to differentiate the two processes. Well, the SNARE receptors form four helix bundles (3 for VAMPs and one for tSNAREs)- although the distribution of helices varies depending on the organ,species) coupled with s peripheral protein like SNAP-25 and coalesce on top of one another. This is usually facilitated by a Ca2+ ion that enters via an ion channel. Here (in the case of enveloped viral membrane fusion, we have a homo trimer that undergoes rearrangement due to the entry of protons from the endosome via Matrix 2 protein as it disrupts the non-covalent interactions that hold the HA2 in its metastable state. So, as you can see, there is a topological difference and beyond that the processes serve different purposes (divergent evolution ?). The thermodynamics of the fusion is a similar but remember that the SNARE action is co-ordinated by the Rab-Rab effector interactions. In short, Mother Nature is creative and beautiful, isn't it ?
I would like an explanation from the 10 people who did not agree with this presentation. If they have alternate opinions or their facts deviate from Harrison. They should have the balls to present them.
Viruses generally make their way across the cell by hijacking,usurping and manipulating the host's microtubules or cytoskeleton (during entry) and the ESCRT machinery (for the release of it's virion progeny. Hope this answers your query .
It depends on whether the catalyst for fusion is receptor-mediated or pH-mediated. If it's just the receptor then it can happen at the plasma membrane but if pH change is needed then fusion occurs in the endosome. Some viruses do both.
The authors of the paper most probably use of PyMol, Chimera and Coot for different parts of the process namely: structure visualization, structure determination and modelling/map refinement. Hope this answers your query.
Good question... I'll try my best to paint you a picture of the process. A) The Influenza virus binds the 2,6 alpha N-acetyl sialic acid-galactose containing receptor on the cell..with the help of the Leucine and Serine in it's active site (of the HA- Hemagglutinin). This is is followed by a conformation change leading to the membrane fusion ,(the plasma membrane and the viral envelope ) facilitated by the HA-2 protein. Consequently, the invagination , endosomal entry and trafficking towards the nucleus. When the pH in the endosome changes to around 5 , the the viral matrix fusion occurs followed by the release of the Nucleoprotein bound RNA, Polymerase and a few proteins. They are transported into the nucleus where gene expression and translation occurs. Remember that the cleavage of the loop of the HA is mediated by Furin protease in the Golgi complex of the cell. Kindly note that such a cleavage is necessary for the virion and the mature virus to be able to enter any cell. Keep in mind that different amino acids line the receptor binding site of HA in different clades and strains. So, the H3N2 HA has an Leu226 while the H1N1 HA has an Aspartate. I hope that this answers your question.
Very interesting; Thank you for preparing such a clear and concise overview of lipid bi layer fusion and process conformations.
What a fantastic lecture. The one I attended at university only managed to confuse me immensely, but now viral membrane fusion is much clearer to me. Thank you so much!
this guy is really good at explaining things, i mean REALLY GOOD!
Well, he has worked on viruses for over 50 years.
Thank you professor, brilliant.
So clear and so useful, thank you
Great presentation -- good cartoons & charts. No-one can tell me that RNA isn't alive! Virus has to be the master of conformational change.
Never realized that ATP and GTP never found outside of the cell (like maybe the ECM).
Have to watch your video 'couple more times and research details.
Thanks, good lookin out.
Very interesting. What are the major differences between these hemagglutinin receptors and the tSNARE and vSNARE receptors used during exocytosis of neurotransmitters?
Nice question..Here's what I know to differentiate the two processes.
Well, the SNARE receptors form four helix bundles (3 for VAMPs and one for tSNAREs)- although the distribution of helices varies depending on the organ,species) coupled with s peripheral protein like SNAP-25 and coalesce on top of one another. This is usually facilitated by a Ca2+ ion that enters via an ion channel.
Here (in the case of enveloped viral membrane fusion, we have a homo trimer that undergoes rearrangement due to the entry of protons from the endosome via Matrix 2 protein as it disrupts the non-covalent interactions that hold the HA2 in its metastable state.
So, as you can see, there is a topological difference and beyond that the processes serve different purposes (divergent evolution ?). The thermodynamics of the fusion is a similar but remember that the SNARE action is co-ordinated by the Rab-Rab effector interactions. In short, Mother Nature is creative and beautiful, isn't it ?
I would like an explanation from the 10 people who did not agree with this presentation. If they have alternate opinions or their facts deviate from Harrison. They should have the balls to present them.
2020, i coming to see this.
How is the movement of virus happen? which energy act behind this?
Viruses generally make their way across the cell by hijacking,usurping and manipulating the host's microtubules or cytoskeleton (during entry) and the ESCRT machinery (for the release of it's virion progeny.
Hope this answers your query .
Does the fusion of membranes occour only at one particular site of endosome and viral membranes or multiple fusion pores are formed b/n the same??
I believe it takes place at one site only.
It depends on whether the catalyst for fusion is receptor-mediated or pH-mediated. If it's just the receptor then it can happen at the plasma membrane but if pH change is needed then fusion occurs in the endosome. Some viruses do both.
Fascinating ! Thanks. Any links to a crash course on protein ribbon representation ?
The authors of the paper most probably use of PyMol, Chimera and Coot for different parts of the process namely: structure visualization, structure determination and modelling/map refinement. Hope this answers your query.
great lecture! but how Influenza gets to the endosome to merge with? I thought there is a plasma membrane on the way
Good question... I'll try my best to paint you a picture of the process.
A) The Influenza virus binds the 2,6 alpha N-acetyl sialic acid-galactose containing receptor on the cell..with the help of the Leucine and Serine in it's active site (of the HA- Hemagglutinin). This is is followed by a conformation change leading to the membrane fusion ,(the plasma membrane and the viral envelope ) facilitated by the HA-2 protein. Consequently, the invagination , endosomal entry and trafficking towards the nucleus. When the pH in the endosome changes to around 5 , the the viral matrix fusion occurs followed by the release of the Nucleoprotein bound RNA, Polymerase and a few proteins. They are transported into the nucleus where gene expression and translation occurs.
Remember that the cleavage of the loop of the HA is mediated by Furin protease in the Golgi complex of the cell. Kindly note that such a cleavage is necessary for the virion and the mature virus to be able to enter any cell.
Keep in mind that different amino acids line the receptor binding site of HA in different clades and strains. So, the H3N2 HA has an Leu226 while the H1N1 HA has an Aspartate.
I hope that this answers your question.
@@Bart_Allen_YT Thank you very much! Amazing explanation!
I7
not good presentation