Taxonomic distribution of proteins containing BAF domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing BAF domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

BAF: roles in chromatin, nuclear structure and retrovirus integration.

Segura-Totten M, Wilson KL
Trends Cell Biol. 2004; 14: 261-6

Barrier-to-autointegration factor (BAF) is an essential protein that ishighly conserved in metazoan evolution. BAF binds directly todouble-stranded DNA, nuclear LEM-domain proteins, lamin A andtranscription activators. BAF is also a host cell component of retroviralpre-integration complexes. BAF binds matrix, a retroviral protein, andfacilitates efficient retroviral DNA integration in vitro through unknownmechanisms. New findings suggest that BAF has structural roles in nuclearassembly and chromatin organization, represses gene expression and mightinterlink chromatin structure, nuclear architecture and gene regulation inmetazoans.

Barrier-to-autointegration factor plays crucial roles in cell cycleprogression and nuclear organization in Drosophila.

Furukawa K, Sugiyama S, Osouda S, Goto H, Inagaki M, Horigome T, Omata S, McConnell M, Fisher PA, Nishida Y
J Cell Sci. 2003; 116: 3811-23

Barrier-to-autointegration factor (BAF) is potentially a DNA-bridgingprotein, which directly associates with inner nuclear membrane proteinscarrying LEM domains. These features point to a key role in regulation ofnuclear function and organization, dependent on interactions between thenuclear envelope and chromatin. To understand the functions of BAF invivo, Drosophila baf null mutants generated by P-element-mediatedimprecise excision were analyzed. Homozygous null mutants showed a typicalmitotic mutant phenotype: lethality at the larval-pupal transition withsmall brains and missing imaginal discs. Mitotic figures were decreasedbut a defined anaphase defect as reported for C. elegans RNAi experimentswas not observed in these small brains, suggesting a different phase orphases of cell cycle arrest. Specific abnormalities in interphase nuclearstructure were frequently found upon electron microscopic examination ofbaf null mutants, with partial clumping of chromatin and convolution ofnuclear shape. At the light microscopic level, grossly aberrant nuclearlamina structure and B-type lamin distribution correlated well with theloss of detectable amounts of BAF protein from nuclei. Together, thesedata represent evidence of BAF's anticipated function in mediatinginteractions between the nuclear envelope and interphase chromosomes. Wethus conclude that BAF plays essential roles in nuclear organization andthat these BAF functions are required in both M phase and interphase ofthe cell cycle.

Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is ahost component of human immunodeficiency virus type 1 virions.

Mansharamani M, Graham DR, Monie D, Lee KK, Hildreth JE, Siliciano RF, Wilson KL
J Virol. 2003; 77: 13084-92

Barrier-to-autointegration factor (BAF) is a conserved human chromatinprotein exploited by retroviruses. Previous investigators showed that BAFbinds double-stranded DNA nonspecifically and is a host component ofpreintegration complexes (PICs) isolated from cells infected with humanimmunodeficiency virus type 1 (HIV-1) or Moloney murine leukemia virus.BAF protects PIC structure and stimulates the integration of salt-strippedPICs into target DNA in vitro. PICs are thought to acquire BAF from thecytoplasm during infection. However, we identified two human tissues (of16 tested) in which BAF mRNA was not detected: thymus and peripheral bloodleukocytes, which are enriched in CD4(+) T lymphocytes and macrophageprecursors, respectively. BAF protein was detected in activated but notresting CD4(+) T lymphocytes; thus, if BAF were essential for PICfunction, we hypothesized that virions might "bring their own BAF."Supporting this model, BAF copurified with HIV-1 virions that weredigested with subtilisin to remove microvesicle contaminants, and BAF waspresent in approximately zero to three copies per virion. In threeindependent assays, BAF bound directly to both p55 Gag (the structuralprecursor of HIV-1 virions) and its cleaved product, matrix. Using lysatesfrom cells overexpressing Gag, endogenous BAF and Gag werecoimmunoprecipitated by antibodies against Gag. Purified recombinant BAFhad low micromolar affinities (1.1 to 1.4 micro M) for recombinant Gag andmatrix. We conclude that BAF is present at low levels in incoming virions,in addition to being acquired from the cytoplasm of newly infected cells.We further conclude that BAF might contribute to the assembly or activityof HIV-1 PICs through direct binding to matrix, as well as DNA.

Solution structure of the cellular factor BAF responsible for protectingretroviral DNA from autointegration.

Cai M, Huang Y, Zheng R, Wei SQ, Ghirlando R, Lee MS, Craigie R, Gronenborn AM, Clore GM
Nat Struct Biol. 1998; 5: 903-9

The solution structure of the human barrier-to-autointegration factor,BAF, a 21,000 Mr dimer, has been solved by NMR, including extensive use ofdipolar couplings which provide a priori long range structuralinformation. BAF is a highly evolutionarily conserved DNA binding proteinthat 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. Thedimer is elongated in shape and the dimer interface comprises principallyhydrophobic contacts supplemented by a single salt bridge. Despite theabsence of any sequence similarity to any other known protein family, thetopology of helices 3-5 is similar to that of a number of DNA bindingproteins, with helices 4 and 5 constituting a helix-turn-helix motif. Amodel for the interaction of BAF with DNA that is consistent withstructural and mutagenesis data is proposed.