Foamy retrovirus integrase contains a Pol dimerization domain required for protease activation.
Unlike orthoretroviruses, foamy retroviruses (FV) synthesize Pol independently of Gag. The FV Pol precursor is cleaved only once between reverse transcriptase (RT) and integrase (IN) by the protease (PR), resulting in a PR-RT and an IN protein. Only the Pol precursor, not the cleaved subunits, is packaged into virions. Like orthoretroviral PRs, FV PR needs to dimerize to be active. Previously, we showed that a Pol mutant lacking IN has defects in PR activity and Pol packaging into virions. We now show that introduction of a leucine zipper (zip) dimerization motif in an IN truncation mutant can restore PR activity, leading to Pol processing in cells. However, these zip mutants neither cleave Gag nor incorporate Pol into virions. We propose that IN is required for Pol dimerization, which is necessary for the creation of a functional PR active site.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Eun-Gyung
EG
Lee
Jacqueline
J
Roy
Dana
D
Jackson
Patrick
P
Clark
Paul L
PL
Boyer
Stephen H
SH
Hughes
Maxine L
ML
Linial
D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D004789:Enzyme Activation; D015684:Gene Products, pol / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015751:Genes, pol; D006801:Humans; D019426:Integrases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016350:Leucine Zippers; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism*; D055503:Protein Multimerization; D053150:Simian foamy virus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D015684:Gene Products, pol; D019426:Integrases; D010447:Peptide Hydrolases