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Cryo-EM Structural Studies of Lentiviral Intasomes


EMSL Project ID
50658

Abstract

A distinct feature of all retroviruses is the ability to integrate their viral DNA (vDNA) into cellular DNA to ensure permanent infection. This process in vivo is catalyzed by the preintegration complex, which is a nucleoprotein complex containing the important viral protein integrase, vDNA, and host cellular protein factors[1]. The retroviral integrase (IN) can form a highly-ordered stable nucleoprotein complex, called an intasome, with vDNA in vitro, which is considered to be the functional counterpart of a preintegration complex that inserts the vDNA into host cell genome. Intasomes are well studied from their biochemical characteristics to their functional structures[2-4]. However, the mechanisms by which they interact with host factors and host chromatin are not well understood. The following outstanding questions remain to be determined: how do intasomes select preferred integration sites in target DNA? How do cellular factors, which retarget integration into active genes, mediate specificity and integrase activity? How does chromatin architecture, including local and global accessibility, affect the process? To address these questions, we are assembling intasome complexes with host factors and mononucleosomes (MNs) and using cryo-EM to understand the structural basis for integration specificity.

Project Details

Start Date
2019-01-14
End Date
2019-10-15
Status
Closed

Team

Principal Investigator

Dmitry Lyumkis
Institution
Salk Institute for Biological Studies

Team Members

Harry Scott
Institution
Oregon Health & Science University

Bo Zhou
Institution
Salk Institute for Biological Studies

Zelin Shan
Institution
Salk Institute for Biological Studies