7z21

Structural highlights

Disease

BAF_HUMAN Defects in BANF1 are the cause of Nestor-Guillermo progeria syndrome (NGPS) [MIM:614008. NGPS is an atypical progeroid syndrome characterized by normal development in the first years of life, later followed by the emergence of generalized lipoatrophy, severe osteoporosis, and marked osteolysis. The atrophic facial subcutaneous fat pad and the marked osteolysis of the maxilla and mandible result in a typical pseudosenile facial appearance with micrognatia, prominent subcutaneous venous patterning, a convex nasal ridge, and proptosis. Cognitive development is completely normal. Patients do not have cardiovascular dysfunction, atherosclerosis, or metabolic anomalies.^[1]

Function

BAF_HUMAN Plays fundamental roles in nuclear assembly, chromatin organization, gene expression and gonad development. May potently compress chromatin structure and be involved in membrane recruitment and chromatin decondensation during nuclear assembly. Contains 2 non-specific dsDNA-binding sites which may promote DNA cross-bridging. Exploited by retroviruses for inhibiting self-destructing autointegration of retroviral DNA, thereby promoting integration of viral DNA into the host chromosome. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD.^{[2] [3] [4]}

References

1. ↑ Puente XS, Quesada V, Osorio FG, Cabanillas R, Cadinanos J, Fraile JM, Ordonez GR, Puente DA, Gutierrez-Fernandez A, Fanjul-Fernandez M, Levy N, Freije JM, Lopez-Otin C. Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am J Hum Genet. 2011 May 13;88(5):650-6. doi: 10.1016/j.ajhg.2011.04.010. Epub, 2011 May 5. PMID:21549337 doi:10.1016/j.ajhg.2011.04.010
2. ↑ Harris D, Engelman A. Both the structure and DNA binding function of the barrier-to-autointegration factor contribute to reconstitution of HIV type 1 integration in vitro. J Biol Chem. 2000 Dec 15;275(50):39671-7. PMID:11005805 doi:10.1074/jbc.M002626200
3. ↑ Segura-Totten M, Kowalski AK, Craigie R, Wilson KL. Barrier-to-autointegration factor: major roles in chromatin decondensation and nuclear assembly. J Cell Biol. 2002 Aug 5;158(3):475-85. Epub 2002 Aug 5. PMID:12163470 doi:10.1083/jcb.200202019
4. ↑ Jacque JM, Stevenson M. The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity. Nature. 2006 Jun 1;441(7093):641-5. Epub 2006 May 7. PMID:16680152 doi:10.1038/nature04682