The BTB/POZ domain (BTB for BR-C, ttk and bab[2] or POZ for Pox virus and Zinc finger[3]) is a
structural domain found in
proteins across the domain
Eukarya.[4] Given its prevalence in eukaryotes and its absence in
Archaea and
bacteria, it likely arose after the origin of eukaryotes.[5] While primarily a protein-protein interaction domain,[5] some BTB domains have additional functionality in
transcriptional regulation,[6]cytoskeletal mobility,[7] protein
ubiquitination and degradation,[8][9][10] and
ion channel formation and operation.[11] BTB domains have traditionally been classified by the other structural features present in the protein.[4]
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.[2] 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.[3]
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.[4] 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.[4] 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.[12]
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.[5]
^Bomont P, Cavalier L, Blondeau F, Ben Hamida C, Belal S, Tazir M, et al. (November 2000). "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.
doi:
10.1038/81701.
PMID11062483.
S2CID2917153.
^Furukawa M, He YJ, Borchers C, Xiong Y (November 2003). "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases". Nature Cell Biology. 5 (11): 1001–1007.
doi:
10.1038/ncb1056.
PMID14528312.
S2CID22937928.