DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV

Publication date: Available online 22 August 2019Source: CellAuthor(s): Danyang Gong, Xinghong Dai, Jonathan Jih, Yun-Tao Liu, Guo-Qiang Bi, Ren Sun, Z. Hong ZhouSummaryAssembly of Kaposi’s sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes (CATCs) and facilitates translocation of an ∼150-kb dsDNA genome, followed by acquisition of a pleomorphic tegument and envelope. Because of deviation from icosahedral symmetry, KSHV portal and tegument structures have largely been obscured in previous studies. Using symmetry-relaxed cryo-EM, we determined the in situ structure of the KSHV portal and its interactions with surrounding capsid proteins, CATCs, and the terminal end of KSHV’s dsDNA genome. Our atomic models of the portal and capsid/CATC, together with visualization of CATCs’ variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Structure-based mutageneses confirm that a triplex deep binding groove for CATCs is a hotspot that holds promise for antiviral development.Graphical Abstract
Source: Cell - Category: Cytology Source Type: research