FMDV 3C: Difference between revisions

(2 intermediate revisions by 2 users not shown)

Line 1:

FMDV 3C Protease

'''Foot and Mouth Disease 3C Protease'''.

'''By, Erica Martel'''

The FMDV viral genome is translated as a single polypeptide precursor that must be cleaved into functional proteins by virally encoded proteases. The FMDV 3C protease is responsible for most cleavages of the viral polyprotein (10 out of the 13 cleavages) and has a highly conserved amino acid sequence across different viral serotypes, making the enzyme an attractive target for inhibitor design and antiviral drugs. The 3C protease cuts itself out of the polyprotein and is responsible for processing the P1 peptide into three viral peptides, VP0 VP3, and VP1. The VP0 peptide is further processed into VP4 and VP2 by an unknown mechanism. To form the FMDV capsid fully processed VPs assemble into a triangular protomer, Figure below. Five protomers come together to make a pentamer, twelve pentamers conjoin to complete the virus shell.

[[Image:FMDV_3C_Prot.jpeg]]

[[Image:FMDV_3C_Prot.jpeg|350px|left|thumb]]

== Function ==

~~FMDV~~ 3C has ~~also~~ been shown to ~~have a number~~ of ~~reported functions on the host cell~~. ~~This includes~~ inhibition of host cell protein synthesis by cleavage of translation initiation factors eIF4A, eIF4G, ~~as well as proteolytic cleavage Histone H3~~, ~~NEMO~~, ~~SAM68~~, and ~~microtubulin associated proteins~~.

The 3C only known function of the viral 3C protease was processing of the viral polyprotein, until recent research discovered interactions with host cell proteins. The 3C protease has been shown to induce proteolytic cleavage of Histone H3. As well as rapid inhibition of host cell protein synthesis by cleavage of translation initiation factors eIF4A, eIF4G between residues E143 and V144.

3C is also able to induce Golgi Fragmentation, causing fragmentation of early, medial, and late Golgi compartments with the most pronounced effect being on early Golgi compartments. Research has found that the Golgi fragments were still able to receive membrane proteins from the endoplasmic reticulum however they were unable to transfer protein to the plasma membrane.

3C has been shown to be able to cleave the C terminus of the nuclear RNA binding protein SAM 68 resulting in redistribution to the cytoplasm. This was particularly interesting because of the fact that Sam68 has been shown to effect FMDV post entry events by interacting with the internal ribosomal entry site within the 5′ non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome.

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
 FMDV 3C Protease
-<StructureSection load='2j92' size='340' side='right' caption='FMDV 3C Protease Type A10' scene=''>
+<StructureSection load='2j92' size='340' side='right' caption='FMDV 3C Protease Type A10 (PDB code [[2j92]])' scene=''>
- '''Foot and Mouth Disease 3C Protease'''.
+'''Foot and Mouth Disease 3C Protease'''.
- '''By, Erica Martel'''
+'''By, Erica Martel'''
 The FMDV viral genome is translated as a single polypeptide precursor that must be cleaved into functional proteins by virally encoded proteases.  The FMDV 3C protease is responsible for most cleavages of the viral polyprotein (10 out of the 13 cleavages) and has a highly conserved amino acid sequence across different viral serotypes, making the enzyme an attractive target for inhibitor design and antiviral drugs. The 3C protease cuts itself out of the polyprotein and is responsible for processing the P1 peptide into three viral peptides, VP0 VP3, and VP1.  The VP0 peptide is further processed into VP4 and VP2 by an unknown mechanism.  To form the FMDV capsid fully processed VPs assemble into a triangular protomer, Figure below. Five protomers come together to make a pentamer, twelve pentamers conjoin to complete the virus shell.
-[[Image:FMDV_3C_Prot.jpeg]]
+[[Image:FMDV_3C_Prot.jpeg|350px|left|thumb]]
 == Function ==
-FMDV 3C has also been shown to have a number of reported functions on the host cell. This includes inhibition of host cell protein synthesis by cleavage of translation initiation factors eIF4A, eIF4G, as well as proteolytic cleavage Histone H3, NEMO, SAM68, and microtubulin associated proteins.
+The 3C only known function of the viral 3C protease was processing of the viral polyprotein, until recent research discovered interactions with host cell proteins. The 3C protease has been shown to induce proteolytic cleavage of Histone H3. As well as rapid inhibition of host cell protein synthesis by cleavage of translation initiation factors eIF4A, eIF4G between residues E143 and V144.
+C is also able to induce Golgi Fragmentation, causing fragmentation of early, medial, and late Golgi compartments with the most pronounced effect being on early Golgi compartments. Research has found that the Golgi fragments were still able to receive membrane proteins from the endoplasmic reticulum however they were unable to transfer protein to the plasma membrane.
+C has been shown to be able to cleave the C terminus of the nuclear RNA binding protein SAM 68 resulting in redistribution to the cytoplasm. This was particularly interesting because of the fact that Sam68 has been shown to effect FMDV post entry events by interacting with the internal ribosomal entry site within the 5′ non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome.