2LZP
Structure of NS2(2-32) GBVB protein
Summary for 2LZP
| Entry DOI | 10.2210/pdb2lzp/pdb |
| NMR Information | BMRB: 18768 |
| Descriptor | NS2 peptide (1 entity in total) |
| Functional Keywords | ns2, gbvb, viral protein |
| Biological source | Hepatitis GB virus B (GBV-B) |
| Cellular location | Core protein: Virion (Potential). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p13: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): Q69422 |
| Total number of polymer chains | 1 |
| Total formula weight | 3370.04 |
| Authors | Montserret, R.,Penin, F.,Martin, A. (deposition date: 2012-10-08, release date: 2014-04-09, Last modification date: 2024-05-15) |
| Primary citation | Boukadida, C.,Marnata, C.,Montserret, R.,Cohen, L.,Blumen, B.,Gouttenoire, J.,Moradpour, D.,Penin, F.,Martin, A. NS2 Proteins of GB Virus B and Hepatitis C Virus Share Common Protease Activities and Membrane Topologies. J.Virol., 88:7426-7444, 2014 Cited by PubMed Abstract: GB virus B (GBV-B), which is hepatotropic in experimentally infected small New World primates, is a member of the Hepacivirus genus but phylogenetically relatively distant from hepatitis C virus (HCV). To gain insights into the role and specificity of hepaciviral nonstructural protein 2 (NS2), which is required for HCV polyprotein processing and particle morphogenesis, we investigated whether NS2 structural and functional features are conserved between HCV and GBV-B. We found that GBV-B NS2, like HCV NS2, has cysteine protease activity responsible for cleavage at the NS2/NS3 junction, and we experimentally confirmed the location of this junction within the viral polyprotein. A model for GBV-B NS2 membrane topology was experimentally established by determining the membrane association properties of NS2 segments fused to green fluorescent protein (GFP) and their nuclear magnetic resonance structures using synthetic peptides as well as by applying an N-glycosylation scanning approach. Similar glycosylation studies confirmed the HCV NS2 organization. Together, our data show that despite limited amino acid sequence similarity, GBV-B and HCV NS2 proteins share a membrane topology with 3 N-terminal transmembrane segments, which is also predicted to apply to other recently discovered hepaciviruses. Based on these data and using trans-complementation systems, we found that intragenotypic hybrid NS2 proteins with heterologous N-terminal membrane segments were able to efficiently trans-complement an assembly-deficient HCV mutant with a point mutation in the NS2 C-terminal domain, while GBV-B/HCV or intergenotypic NS2 chimeras were not. These studies indicate that virus- and genotype-specific intramolecular interactions between N- and C-terminal domains of NS2 are critically involved in HCV morphogenesis. PubMed: 24741107DOI: 10.1128/JVI.00656-14 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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