1zh1

From Proteopedia

Revision as of 05:19, 21 November 2007

Structure of the zinc-binding domain of HCV NS5A

Overview

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.

About this Structure

1ZH1 is a Single protein structure of sequence from Hepatitis c virus with ZN as ligand. Full crystallographic information is available from OCA.

Reference

Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase., Tellinghuisen TL, Marcotrigiano J, Rice CM, Nature. 2005 May 19;435(7040):374-9. PMID:15902263

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