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Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein

Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein
Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein
Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. The first open reading frame of the norovirus RNA genome encodes for a polyprotein that is cleaved by the viral protease into six non-structural proteins. The first non-structural protein, NS1-2, lacks any significant sequence similarity to other viral or cellular proteins and limited information is available about the function and biophysical characteristics of this protein. Bioinformatic analyses identified an inherently disordered region (residues 1-142) in the highly divergent N-terminal region of the norovirus NS1-2 protein. Expression and purification of the NS1-2 protein of Murine norovirus confirmed these predictions by identifying several features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-2 protein also identified the presence of an NS1-2 dimer in Escherichia coli and transfected HEK293T cells. Inherent disorder provides significant advantages including structural flexibility and the ability to bind to numerous targets allowing a single protein to have multiple functions. These advantages combined with the potential functional advantages of multimerisation suggest a multi-functional role for the NS1-2 protein.
1932-6203
e30534-[13pp]
Baker, Estelle S.
ed1ab3db-d5db-46a1-ad43-a68a22641f95
Luckner, Sylvia R.
d43ca68e-1360-4d8c-bac1-e7de3e96f1e7
Krause, Kurt L.
203d541b-70fc-4217-9d0d-8b4225f27d33
Lambden, Paul R.
4fcd536e-2d9a-4366-97c6-386e6b005698
Clarke, Ian N.
ff6c9324-3547-4039-bb2c-10c0b3327a8b
Ward, Vernon K.
3dbf2165-fec7-437f-af39-693ea61ca31f
Baker, Estelle S.
ed1ab3db-d5db-46a1-ad43-a68a22641f95
Luckner, Sylvia R.
d43ca68e-1360-4d8c-bac1-e7de3e96f1e7
Krause, Kurt L.
203d541b-70fc-4217-9d0d-8b4225f27d33
Lambden, Paul R.
4fcd536e-2d9a-4366-97c6-386e6b005698
Clarke, Ian N.
ff6c9324-3547-4039-bb2c-10c0b3327a8b
Ward, Vernon K.
3dbf2165-fec7-437f-af39-693ea61ca31f

Baker, Estelle S., Luckner, Sylvia R., Krause, Kurt L., Lambden, Paul R., Clarke, Ian N. and Ward, Vernon K. (2012) Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein. PLoS ONE, 7 (2), e30534-[13pp]. (doi:10.1371/journal.pone.0030534). (PMID:22347381)

Record type: Article

Abstract

Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. The first open reading frame of the norovirus RNA genome encodes for a polyprotein that is cleaved by the viral protease into six non-structural proteins. The first non-structural protein, NS1-2, lacks any significant sequence similarity to other viral or cellular proteins and limited information is available about the function and biophysical characteristics of this protein. Bioinformatic analyses identified an inherently disordered region (residues 1-142) in the highly divergent N-terminal region of the norovirus NS1-2 protein. Expression and purification of the NS1-2 protein of Murine norovirus confirmed these predictions by identifying several features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-2 protein also identified the presence of an NS1-2 dimer in Escherichia coli and transfected HEK293T cells. Inherent disorder provides significant advantages including structural flexibility and the ability to bind to numerous targets allowing a single protein to have multiple functions. These advantages combined with the potential functional advantages of multimerisation suggest a multi-functional role for the NS1-2 protein.

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Published date: 7 February 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337340
URI: https://eprints.soton.ac.uk/id/eprint/337340
ISSN: 1932-6203
PURE UUID: 8bc160bc-2922-41cc-86ab-26ab06f36121
ORCID for Ian N. Clarke: ORCID iD orcid.org/0000-0002-4938-1620

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Date deposited: 24 Apr 2012 13:07
Last modified: 06 Jun 2018 13:19

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