TY - JOUR
T1 - Cryo-EM structure of the HIV-1 Pol polyprotein provides insights into virion maturation
AU - Harrison, Jerry Joe E.K.
AU - Passos, Dario Oliveira
AU - Bruhn, Jessica F.
AU - Bauman, Joseph D.
AU - Tuberty, Lynda
AU - DeStefano, Jeffrey J.
AU - Ruiz, Francesc Xavier
AU - Lyumkis, Dmitry
AU - Arnold, Eddy
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/7
Y1 - 2022/7
N2 - Key proteins of retroviruses and other RNA viruses are translated and subsequently processed from polyprotein precursors by the viral protease (PR). Processing of the HIV Gag-Pol polyprotein yields the HIV structural proteins and enzymes. Structures of the mature enzymes PR, reverse transcriptase (RT), and integrase (IN) aided understanding of catalysis and design of antiretrovirals, but knowledge of the Pol precursor architecture and function before PR cleavage is limited. We developed a system to produce stable HIV-1 Pol and determined its cryo-electron microscopy structure. RT in Pol has a similar arrangement to the mature RT heterodimer, and its dimerization may draw together two PR monomers to activate proteolytic processing. HIV-1 thus may leverage the dimerization interfaces in Pol to regulate assembly and maturation of polyprotein precursors.
AB - Key proteins of retroviruses and other RNA viruses are translated and subsequently processed from polyprotein precursors by the viral protease (PR). Processing of the HIV Gag-Pol polyprotein yields the HIV structural proteins and enzymes. Structures of the mature enzymes PR, reverse transcriptase (RT), and integrase (IN) aided understanding of catalysis and design of antiretrovirals, but knowledge of the Pol precursor architecture and function before PR cleavage is limited. We developed a system to produce stable HIV-1 Pol and determined its cryo-electron microscopy structure. RT in Pol has a similar arrangement to the mature RT heterodimer, and its dimerization may draw together two PR monomers to activate proteolytic processing. HIV-1 thus may leverage the dimerization interfaces in Pol to regulate assembly and maturation of polyprotein precursors.
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U2 - 10.1126/sciadv.abn9874
DO - 10.1126/sciadv.abn9874
M3 - Article
C2 - 35857464
AN - SCOPUS:85133843530
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 27
M1 - abn9874
ER -