title: The linker region of NS3 plays a critical role in the replication and infectivity of hepatitis C virus.
abstract: Hepatitis C virus (HCV) NS3-4A is required for viral replication and assembly. We establish that virus assembly is sensitive to mutations in the linker region between the helicase and protease domains of NS3-4A. However, we find that the protease cleavage, RNA binding, and unwinding rates of NS3 are minimally affected in vitro. Thus, we conclude that the NS3 linker is critical for mediating protein-protein interactions and dynamic control rather than for modulating the enzymatic functions of NS3-4A.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
authors: Andrew
authors: A
authors: Kohlway
authors: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA.
authors: Nathan
authors: N
authors: Pirakitikulr
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
authors: Steve C
authors: SC
authors: Ding
authors: Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut, USA.
authors: Feng
authors: F
authors: Yang
authors: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA.
authors: Dahai
authors: D
authors: Luo
authors: Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut, USA.
authors: Brett D
authors: BD
authors: Lindenbach
authors: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA Department of Chemistry, Yale University, New Haven, Connecticut, USA Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA anna.pyle@yale.edu.
authors: Anna M
authors: AM
authors: Pyle
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus