1ZH1

Structure of the zinc-binding domain of HCV NS5A

Summary for 1ZH1

• Entry DOI: 10.2210/pdb1zh1/pdb
• Descriptor: non-structural polyprotein, ZINC ION (3 entities in total)
• Functional Keywords: hcv, nonstructural protein 5a, ns5a, domain i, metal binding protein
• Biological source: Hepatitis C virus
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: 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): Q9WMX2
• Total number of polymer chains: 2
• Total formula weight: 36147.79

Authors

Tellinghuisen, T.L.,Marcotrigiano, J.,Rice, C.M. (deposition date: 2005-04-22, release date: 2005-05-24, Last modification date: 2024-10-16)

Primary citation

Tellinghuisen, T.L.,Marcotrigiano, J.,Rice, C.M.
Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase.
Nature, 435:374-379, 2005

PubMed Abstract: Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world's population. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a multi-subunit membrane-associated complex. The non-structural protein NS5A is an active component of HCV replicase, as well as a pivotal regulator of replication and a modulator of cellular processes ranging from innate immunity to dysregulated cell growth. NS5A is a large phosphoprotein (56-58 kDa) with an amphipathic alpha-helix at its amino terminus that promotes membrane association. After this helix region, NS5A is organized into three domains. The N-terminal domain (domain I) coordinates a single zinc atom per protein molecule. Mutations disrupting either the membrane anchor or zinc binding of NS5A are lethal for RNA replication. However, probing the role of NS5A in replication has been hampered by a lack of structural information about this multifunctional protein. Here we report the structure of NS5A domain I at 2.5-A resolution, which contains a novel fold, a new zinc-coordination motif and a disulphide bond. We use molecular surface analysis to suggest the location of protein-, RNA- and membrane-interaction sites.

PubMed: 15902263
DOI: 10.1038/nature03580

Experimental method

X-RAY DIFFRACTION (2.5 Å)