BTB/POZ domain explained

The BTB/POZ domain (BTB for BR-C, ttk and bab[1] or POZ for Pox virus and Zinc finger[2]) is a structural domain found in proteins across the domain Eukarya.[3] Given its prevalence in eukaryotes and its absence in Archaea and bacteria, it likely arose after the origin of eukaryotes.[4] While primarily a protein-protein interaction domain,[4] some BTB domains have additional functionality in transcriptional regulation,[5] cytoskeletal mobility,[6] protein ubiquitination and degradation,[7] [8] [9] and ion channel formation and operation.[10] BTB domains have traditionally been classified by the other structural features present in the protein.

Discovery

The BTB/POZ domain was first described by two independent research groups in 1994. Researchers at UCLA found a conserved 115 amino acid motif in nine Drosophila proteins, including Broad complex, tramtrack, and bric-a-brac, and labelled the conserved region the BTB domain.[1] At the same time, a group at Imperial Cancer Research Fund Laboratories in London discovered the same 120 amino acid motif in a set of otherwise unrelated zinc finger proteins and a set of pox-virus proteins, and thus named the region the POZ domain.[2]

Structure

The motif is approximately 120 amino acids long, with a core fold of 95 amino acids that form five alpha helices and three beta sheets.[3] The alpha helices form two hairpin structures, A1/A2 and A4/A5, out of the first and second and the fourth and fifth alpha helices respectively. The remaining alpha helix, A3, bridges the two. The three beta sheets cap the A1/A2 hairpin. Additional secondary structures can surround this core fold. For example, BTB domains in Kelch proteins, C2H2 zinc finger proteins, and HTH-containing proteins frequently include an additional alpha helix and beta sheet at the N-terminus of the domain.[11]

Function

The BTB domain is primarily a protein-protein interaction domain. In zinc-finger proteins, it commonly forms homodimers with other BTB domains, mediates heteromeric dimerization, and recruits transcriptional corepressors.[4]

Notes and References

  1. Zollman S, Godt D, Privé GG, Couderc JL, Laski FA . The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila . Proceedings of the National Academy of Sciences of the United States of America . 91 . 22 . 10717–10721 . October 1994 . 7938017 . 45093 . 10.1073/pnas.91.22.10717 . 1994PNAS...9110717Z . free .
  2. Bardwell VJ, Treisman R . The POZ domain: a conserved protein-protein interaction motif . Genes & Development . 8 . 14 . 1664–1677 . July 1994 . 7958847 . 10.1101/gad.8.14.1664 . 27334252 . free .
  3. Stogios PJ, Downs GS, Jauhal JJ, Nandra SK, Privé GG . Sequence and structural analysis of BTB domain proteins . Genome Biology . 6 . 10 . R82 . 2005-09-15 . 16207353 . 1257465 . 10.1186/gb-2005-6-10-r82 . free .
  4. Perez-Torrado R, Yamada D, Defossez PA . Born to bind: the BTB protein-protein interaction domain . BioEssays . 28 . 12 . 1194–1202 . December 2006 . 17120193 . 10.1002/bies.20500 . 23248814 .
  5. Melnick A, Ahmad KF, Arai S, Polinger A, Ball H, Borden KL, Carlile GW, Prive GG, Licht JD . 6 . In-depth mutational analysis of the promyelocytic leukemia zinc finger BTB/POZ domain reveals motifs and residues required for biological and transcriptional functions . Molecular and Cellular Biology . 20 . 17 . 6550–6567 . September 2000 . 10938130 . 86130 . 10.1128/MCB.20.17.6550-6567.2000 .
  6. Bomont P, Cavalier L, Blondeau F, Ben Hamida C, Belal S, Tazir M, Demir E, Topaloglu H, Korinthenberg R, Tüysüz B, Landrieu P, Hentati F, Koenig M . 6 . The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy . Nature Genetics . 26 . 3 . 370–374 . November 2000 . 11062483 . 10.1038/81701 . 2917153 .
  7. Furukawa M, He YJ, Borchers C, Xiong Y . Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases . Nature Cell Biology . 5 . 11 . 1001–1007 . November 2003 . 14528312 . 10.1038/ncb1056 . 22937928 .
  8. Pintard L, Willis JH, Willems A, Johnson JL, Srayko M, Kurz T, Glaser S, Mains PE, Tyers M, Bowerman B, Peter M . 6 . The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase . Nature . 425 . 6955 . 311–316 . September 2003 . 13679921 . 10.1038/nature01959 . 2003Natur.425..311P . 4425748 .
  9. Geyer R, Wee S, Anderson S, Yates J, Wolf DA . BTB/POZ domain proteins are putative substrate adaptors for cullin 3 ubiquitin ligases . Molecular Cell . 12 . 3 . 783–790 . September 2003 . 14527422 . 10.1016/s1097-2765(03)00341-1 . free .
  10. Minor DL, Lin YF, Mobley BC, Avelar A, Jan YN, Jan LY, Berger JM . The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel . Cell . 102 . 5 . 657–670 . September 2000 . 11007484 . 10.1016/s0092-8674(00)00088-x . 776305 . free .
  11. Bonchuk A, Balagurov K, Georgiev P . BTB domains: A structural view of evolution, multimerization, and protein-protein interactions . BioEssays . 45 . 2 . e2200179 . February 2023 . 36449605 . 10.1002/bies.202200179 . 254122488 .

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