Structural highlights
Disease
BCL6_HUMAN Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
Function
BCL6_HUMAN Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.[1] [2]
Publication Abstract from PubMed
B cell lymphoma 6 (BCL6) is a transcriptional repressor that is deregulated in diffuse large B cell lymphoma, and the peptide aptamer, Apt48, inhibits BCL6 by an unknown mechanism. We report the crystal structure of BCL6 in complex with an Apt48 peptide, and show that Apt48 binds to a therapeutically uncharacterized region at the bottom of the BCL6 BTB domain. We show that the corepressor binding site of the BTB domain may be divided conceptually into two low-affinity, peptide-binding regions. An upper region, the lateral groove, binds peptides in robust three-dimensional conformations, whereas a lower binding site is permissive to less-specific interactions. We show that, even with little sequence specificity, the interactions of the lower region are required for the high-affinity binding of the SMRT corepressor and other peptides to the BTB domain. This has relevance for the design of new BCL6 inhibitors and for understanding the evolution of corepressor interactions with the BTB domain.
Structural basis of Apt48 inhibition of the BCL6 BTB domain.,Zacharchenko T, Kalverda AP, Wright SC Structure. 2022 Mar 3;30(3):396-407.e3. doi: 10.1016/j.str.2021.10.010. Epub 2021 , Nov 12. PMID:34774129[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Niu H, Ye BH, Dalla-Favera R. Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 1998 Jul 1;12(13):1953-61. PMID:9649500
- ↑ Ghetu AF, Corcoran CM, Cerchietti L, Bardwell VJ, Melnick A, Prive GG. Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol Cell. 2008 Feb 15;29(3):384-91. PMID:18280243 doi:10.1016/j.molcel.2007.12.026
- ↑ Zacharchenko T, Kalverda AP, Wright SC. Structural basis of Apt48 inhibition of the BCL6 BTB domain. Structure. 2022 Mar 3;30(3):396-407.e3. PMID:34774129 doi:10.1016/j.str.2021.10.010
