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2M9U

Solution NMR structure of the C-terminal domain (CTD) of Moloney murine leukemia virus integrase, Northeast Structural Genomics Target OR41A

Summary for 2M9U
Entry DOI10.2210/pdb2m9u/pdb
NMR InformationBMRB: 19299
DescriptorIntegrase p46 (1 entity in total)
Functional Keywordssh3 domain, nesg, or41a-15.1, psi-biology, northeast structural genomics consortium, viral protein
Biological sourceMoloney murine leukemia virus isolate Shinnick
Cellular locationGag-Pol polyprotein: Host cell membrane; Lipid-anchor (Potential). Matrix protein p15: Virion (Potential). Capsid protein p30: Virion (Potential). Nucleocapsid protein p10: Virion (Potential): P03355
Total number of polymer chains1
Total formula weight10131.59
Authors
Aiyer, S.,Rossi, P.,Schneider, W.M.,Chander, A.,Roth, M.J.,Montelione, G.T.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2013-06-19, release date: 2013-12-18, Last modification date: 2024-05-15)
Primary citationAiyer, S.,Swapna, G.V.,Malani, N.,Aramini, J.M.,Schneider, W.M.,Plumb, M.R.,Ghanem, M.,Larue, R.C.,Sharma, A.,Studamire, B.,Kvaratskhelia, M.,Bushman, F.D.,Montelione, G.T.,Roth, M.J.
Altering murine leukemia virus integration through disruption of the integrase and BET protein family interaction.
Nucleic Acids Res., 42:5917-5928, 2014
Cited by
PubMed Abstract: We report alterations to the murine leukemia virus (MLV) integrase (IN) protein that successfully result in decreasing its integration frequency at transcription start sites and CpG islands, thereby reducing the potential for insertional activation. The host bromo and extraterminal (BET) proteins Brd2, 3 and 4 interact with the MLV IN protein primarily through the BET protein ET domain. Using solution NMR, protein interaction studies, and next generation sequencing, we show that the C-terminal tail peptide region of MLV IN is important for the interaction with BET proteins and that disruption of this interaction through truncation mutations affects the global targeting profile of MLV vectors. The use of the unstructured tails of gammaretroviral INs to direct association with complexes at active promoters parallels that used by histones and RNA polymerase II. Viruses bearing MLV IN C-terminal truncations can provide new avenues to improve the safety profile of gammaretroviral vectors for human gene therapy.
PubMed: 24623816
DOI: 10.1093/nar/gku175
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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