Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration.
The solution structure of the human barrier-to-autointegration factor, BAF, a 21,000 Mr dimer, has been solved by NMR, including extensive use of dipolar couplings which provide a priori long range structural information. BAF is a highly evolutionarily conserved DNA binding protein that is responsible for inhibiting autointegration of retroviral DNA, thereby promoting integration of retroviral DNA into the host chromosome. BAF is largely helical, and each subunit is composed of five helices. The dimer is elongated in shape and the dimer interface comprises principally hydrophobic contacts supplemented by a single salt bridge. Despite the absence of any sequence similarity to any other known protein family, the topology of helices 3-5 is similar to that of a number of DNA binding proteins, with helices 4 and 5 constituting a helix-turn-helix motif. A model for the interaction of BAF with DNA that is consistent with structural and mutagenesis data is proposed.
Cai
M
M
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
Huang
Y
Y
Zheng
R
R
Wei
S Q
SQ
Ghirlando
R
R
Lee
M S
MS
Craigie
R
R
Gronenborn
A M
AM
Clore
G M
GM
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D019077:Helix-Turn-Helix Motifs; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D012190:Retroviridae / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D016662:Virus Integration / Q000502:physiology
C501959:BANF1 protein, human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA