Title: Identification of residues in the C-terminal domain of HIV-1 integrase that mediate binding to TRN-SR2
Authors: De Houwer, St├ęphanie
Demeulemeester, Jonas
Thys, Wannes
Taltynov, Oliver
Christ, Frauke
Debyser, Zeger # ×
Issue Date: Aug-2012
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:287 issue:4 pages:34059-34068
Abstract: Transportin-SR2 (TRN-SR2, TNPO3) is a cellular cofactor of HIV replication that has been implicated in the nuclear import of HIV. TRN-SR2 was originally identified in a yeast two-hybrid screen as an interaction partner of HIV integrase (IN) and in two independent siRNA screens as a co-factor of viral replication. We now studied the interaction of TRN-SR2 and HIV IN in molecular detail and identified the TRN-SR2 interacting regions of IN. A weak interaction with the catalytic core domain (CCD) and a strong interaction with the C-terminal domain (CTD) of IN were detected. By dissecting the catalytic core domain (CCD) of IN into short structural fragments we identified a peptide (INIP1, aa 170-EHLKTAVQMAVFIHNFKRKGGI-191) retaining the ability to interact with TRN-SR2. By dissecting the C-terminal domain (CTD) of IN we could identify two interacting peptides (aa 214-QKQITKIQNFRVYYR-229 and 262-RRKVKIIRDYGK-274) that come together in the CTD tertiary structure to form an exposed antiparallel β-sheet. Through site specific mutagenesis we defined following sets of amino acids in IN as important for the interaction with TRN-SR2: F185/K186/R187/K188 in the CCD and R262/R263/K264 and K266/R269 in the CTD. An HIV-1 strain carrying K266A/R269A in IN was replication defective due to a block in reverse transcription, confounding the study of nuclear import. Insight into the IN/TRN-SR2 interaction interface is necessary to guide drug discovery efforts targeting the nuclear entry step of replication.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
De Houwer.full.pdf Published 2071KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science