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Structure determination of diversity-generating retroelements ribonucleoprotein complex by Cryo-EM


EMSL Project ID
51273

Abstract

Diversity-generating retroelements (DGRs) are unique and unparalleled generators of massive protein sequence diversity. DGRs diversify proteins through a fundamentally different mechanism than the vertebrate immune system. In DGRs, diversification arises from genetic information being transmitted unfaithfully. This occurs during reverse transcription from RNA to cDNA, and the infidelity towards adenine shapes the pattern of protein functional variation. This selective infidelity to adenines is the central hallmark feature of DGRs. We have found that the Bordetella bacteriophage DGR reverse transcriptase bRT in complex with the accessory variability determinant (Avd) protein is sufficient to synthesize adenine-mutagenized cDNA. Our results indicate that bRT-Avd and the DGR RNA forms a functional and structured ribonucleoprotein (RNP) particle. We are on the verge of uncovering the molecular and atomic details underlying selective infidelity through the visualization of bRT-Avd/RNA complexes in different functional states by Cryo-EM. Our proposed studies will provide fundamental advances in understanding DGRs.

Project Details

Start Date
2020-02-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Partho Ghosh
Institution
University of California, San Diego

Team Members

Sumit Handa
Institution
University of California, San Diego

Janette Myers
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory