Research - SOLARIS National Synchrotron Radiation Centre - Jagiellonian University

Retrovirus research using Cryo-EM

Reverse transcription involves the conversion of single-stranded RNA to double-stranded DNA. This is a key step in the replication of retroviruses, catalyzed by the enzyme reverse transcriptase. Retroviruses are divided into two subfamilies, one of which, Spumaretrovirinae, has a different proliferation cycle and a different reverse transcriptase domain structure. The presented studies provide the first structural description of the nucleic acid binding by viral reverse transferase, demonstrating its ability to change the oligomeric state depending on the type of bound nucleic acid.

Reverse transcriptases (RTs) use their DNA polymerase and RNase H activities to catalyze the conversion of single-stranded RNA to double-stranded DNA, a crucial process for the replication of retroviruses. Foamy viruses (FV) possess a unique RT which is a fusion with the protease (PR) domain. The mechanism of substrate binding by this enzyme has been unknown. The authors report a crystal structure of monomeric full-length marmoset FV (MFV) PR-RT in complex with an RNA/DNA hybrid substrate. Moreover, the describtion of a structure of MFV PR-RT with RNase H deletion in complex with a dsDNA substrate in which the enzyme forms an asymmetric homodimer has been presented. Cryo-electron microscopy reconstruction of full-length MFV PR-RT - dsDNA complex confirmed the dimeric architecture. These findings represent the first structural description of nucleic acid binding by a foamy viral RT and demonstrate its ability to change its oligomeric state depending on the type of bound nucleic acid.

The conducted research, once again, confirms the extraordinary usefulness of electron cryomicroscopy and its significant contribution to the development of structural biology. The use of Cryo-EM in March 2020 turned out to be very important, when scientists solved the structure of the coronavirus spike protein, which allowed doctors and scientists to fight Covid-19. The work was published in Nature.

Full version of the publication you can find here.

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Modification date 11/04/2022 - Agnieszka Cudek

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