Investigation of the Multimerization Region of the Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Protein K-bZIP: the Proposed Leucine Zipper Region Encodes a Multimerization Domain with an Unusual Structure

Abstract

The K8 gene of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) shares many functional similarities with the BZLF1 gene of Epstein-Barr virus. The protein products of K8 and BZLF1, K-bZIP (RAP, K8) and Zta (BZLF1, ZEBRA, Z) have both been proposed to be members of the bZIP family of transcription factors, forming multimers via a coiled-coil motif termed a leucine zipper. Substantial evidence supporting this model for Zta is published. Here, we demonstrate that the proposed leucine zipper region of K-bZIP (amino acids 182 to 218) is required for multimer formation but that it does not fold as a coiled coil.

Leucine Zipper Domain Is Required for Kaposi Sarcoma-associated Herpesvirus (KSHV) K-bZIP Protein to Interact with Histone Deacetylase and Is Important for KSHV Replication

“…2 is associated with Kaposi sarcoma (1,2) and several B cell malignancies, such as primary effusion lymphoma and multicentric Castleman disease (1,(3)(4)(5)(6). Cell types identified for successful KSHV infection include monocytes, endothelial/spindle cells, B cells, and epithelial cells (6 -11).…”

Kaposi's Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That Regulates Viral DNA Replication in Coordination with a Noncoding RNA

“…Based on its homology to Epstein-Barr virus (EBV) ZTA protein, K8 protein is divided into three domains: the transactional domain at the N terminus (amino acids [aa] 1 to 121) (32), the basic domain (DNA binding domain; aa 121 to 189) (23), and a leucine zipper domain at its C terminus (aa 189 to 237) ( Fig. 5A) (31,33,34). To identify the domain(s) in K8 that is required for RNA binding, a series of truncation and deletion mutants of K8 were constructed and examined for RNA binding ability in a biotinylated RNA pulldown assay.…”

Initiation of Lytic DNA Replication in Epstein–Barr Virus: Search for a Common Family Mechanism

“…By contrast, the overexpression of EBV Rta is unable to rescue a BZLF1 -knockout virus [107]. K8 also differs from Zta in that its ‘zipper’ region (residues 190–237), while required for multimerization [108], folds into a β-sheet rather than as an α-helix [109]. K8 can bind to Rta via its zipper motif and this interaction may attenuate Rta transcription activity and, consequently, activate its replication function [103,110].…”