NF-Y Transcription Factor Sandbox

From Proteopedia

Revision as of 02:01, 7 November 2013

Template:STRUCTURE 4awl

Protein Function

NF-Y is a transcription factor (TF), which is a protein that binds to specific DNA sequences, controlling the flow of genetic information from DNA into messenger RNA (mRNA), which leads to the formation of proteins. NF-Y is an important protein involved in histone posttranslational modifications (PTMs) ^[1]. These PTMs aid in regions of the DNA that are destined to be transcribed. NF-Y is also involved in recruiting enzymes responsible for acetylations on active promoters, suggesting that NF-Y is involved in switch-modifications (reference here). Furthermore, NF-Y is a sequence-specific TF. It is possible that NF-Y and other sequence-specific TFs determine histone modifications on promoters.
NF-Y has two isoforms, which differ in the amount of amino acids in the Q-rich activation domain. The purpose of these isoforms has yet to be seen, however studies suggest that certain gene expression is dependent on which isoform is present at a time. Another study showed that NF-YA and NF-YB is required for embryonic stem cell (ESC) viability (reference hereee).
NF-Y is regulated by redox mechanisms. The regulated subunit (NF-YB) has three conserved cysteines in its A2 helix: , , and C103; which sense the cellular redox potential and allow heterodimerization under reduced conditions. In oxidized conditions, NF-YB forms heterodimers in the cytoplasm which hinders CCAAT-binding and transcriptional activation(reference).

Protein Structure

NF-Y transcription factor consists of , , and subunits. NF-YA subunit contains two α-helices, NF-YB subunit contains four α-helices and two β-sheets, and NF-YC subunit contains three α-helices and two β-sheets. The NF-YB and NF-YC subunits each contain a histone fold motif and form a NF-YB/NF-YC heterodimer^[2]. One of the two α helices of the NF-YA subunit, the N terminal , interacts with NF-YB/NF-YC heterodimer resulting in a heterotrimer. The NF-Y heterotrimer is stabilized by ionic interactions, interactions between the backbone atoms of residues, and hydrophobic residues. Stabilizing ionic interactions occur between Asn239(NF-YA) with Asp109(NF-YC) and Asp112(NF-YC)^[1]. Residue backbone interactions occur between Leu123(NF-YB) with Phe113(NF-YC), Arg245(NF-YA) with Glu98(NF-YB) and Glu101(NF-YB), Arg249(NF-YA) with Glu90(NF-YB), and Arg250(NF-YA) with Asp116(NF-YC)^[1]. Hydrophobic residues that contribute to the stabilization of the NF-Y heterotrimer are only located at NF-YA and NF-YB subunits at residues Ile246(NF-YA), Phe94(NF-YB), and Ile115(NF-YB)^[1]. The NF-Y heterotrimer is also stabilized by the segment through intramolecular interactions of NF-YA residues on the main chain and side chain. Along with stabilization, the A1A2 linker provides the flexibility needed to direct the NF-YA chain toward DNA^[1].

Interaction With DNA

The C terminal of the NF-YA subunit inserts deep into the minor groove of DNA. NF-YA A2 helix binds to the box and causes the minor groove to widen at the CCAAT box. An important residue in the catalytic site is

References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4} Nardini M, Gnesutta N, Donati G, Gatta R, Forni C, Fossati A, Vonrhein C, Moras D, Romier C, Bolognesi M, Mantovani R. Sequence-Specific Transcription Factor NF-Y Displays Histone-like DNA Binding and H2B-like Ubiquitination. Cell. 2013 Jan 17;152(1-2):132-43. doi: 10.1016/j.cell.2012.11.047. PMID:23332751 doi:http://dx.doi.org/10.1016/j.cell.2012.11.047
2. ↑ Xiao J, Zhou Y, Lai H, Lei S, Chi LH, Mo X. Transcription Factor NF-Y Is a Functional Regulator of the Transcription of Core Clock Gene Bmal1. J Biol Chem. 2013 Nov 1;288(44):31930-6. doi: 10.1074/jbc.M113.507038. Epub 2013 , Sep 12. PMID:24030830 doi:http://dx.doi.org/10.1074/jbc.M113.507038