PDBsum entry 2m0s

Viral protein

PDB id: 2m0s

Contents

Protein chain

28 a.a.

PDB id:

2m0s

Name:

Viral protein

Title:

Solution structure of the trans-membrane domain of the ns2a of dengue virus

Structure:

Ns2a protein. Chain: a. Fragment: unp residues 1194-1221. Engineered: yes

Source:

Synthetic: yes. Dengue virus 2. Organism_taxid: 11060

NMR struc:

10 models

Authors:

S.Gayen,C.Kang

Key ref:

X.Xie et al. (2013). Membrane topology and function of dengue virus NS2A protein. J Virol, 87, 4609-4622. PubMed id: 23408612 DOI: 10.1128/JVI.02424-12

Date:

05-Nov-12 Release date: 27-Feb-13

Protein chain

Q9YKL3  (Q9YKL3_9FLAV) -  Genome polyprotein from dengue virus type 2

Seq: 3391 a.a.

Struc: 28 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.4.21.91 - flavivirin.
• Reaction: Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.
• Enzyme class 2: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺
• Enzyme class 3: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1128/JVI.02424-12

J Virol 87:4609-4622 (2013)

PubMed id: 23408612

Membrane topology and function of dengue virus NS2A protein.

X.Xie, S.Gayen, C.Kang, Z.Yuan, P.Y.Shi.

ABSTRACT

Flavivirus nonstructural protein 2A (NS2A) is a component of the viral replication complex that functions in virion assembly and antagonizes the host immune response. Although flavivirus NS2A is known to associate with the endoplasmic reticulum (ER) membrane, the detailed topology of this protein has not been determined. Here we report the first topology model of flavivirus NS2A on the ER membrane. Using dengue virus (DENV) NS2A as a model, we show that (i) the N-terminal 68 amino acids are located in the ER lumen, with one segment (amino acids 30 to 52) that interacts with ER membrane without traversing the lipid bilayer; (ii) amino acids 69 to 209 form five transmembrane segments, each of which integrally spans the ER membrane; and (iii) the C-terminal tail (amino acids 210 to 218) is located in the cytosol. Nuclear magnetic resonance (NMR) structural analysis showed that the first membrane-spanning segment (amino acids 69 to 93) consists of two helices separated by a "helix breaker." The helix breaker is formed by amino acid P85 and one positively charged residue, R84. Functional analysis using replicon and genome-length RNAs of DENV-2 indicates that P85 is not important for viral replication. However, when R84 was replaced with E, the mutation attenuated both viral RNA synthesis and virus production. Remarkably, an R84A mutation did not affect viral RNA synthesis but blocked intracellular formation of infectious virions. Collectively, the mutagenesis results demonstrate that NS2A functions in both DENV RNA synthesis and virion assembly/maturation. The topology model of DENV NS2A provides a good starting point for studying how flavivirus NS2A modulates viral replication and evasion of host immune response.