PMID- 25098749
OWN - NLM
STAT- MEDLINE
DCOM- 20150827
LR  - 20140819
IS  - 1520-4898 (Electronic)
IS  - 0001-4842 (Linking)
VI  - 47
IP  - 8
DP  - 2014 Aug 19
TI  - Structural metal sites in nonclassical zinc finger proteins involved in 
      transcriptional and translational regulation.
PG  - 2643-50
LID - 10.1021/ar500182d [doi]
AB  - Zinc finger (ZF) proteins are a large family of metalloproteins that utilize zinc 
      for structural purposes. Zinc coordinates to a combination of cysteine thiol and 
      histidine imidazole residues within the ZF polypeptide sequence resulting in a 
      folded and functional protein. Initially, a single class of ZFs were identified. 
      These ZFs, now referred to as the "classical" ZFs, utilize a Cys2His2 (CCHH) 
      ligand set to bind zinc. Upon Zn coordination, the classical ZFs fold into a 
      structure made up of an alpha helix and an antiparallel beta sheet. When folded, 
      classical ZFs recognize and bind to specific DNA targets and function as 
      transcription factors. With the advent of genome sequencing and proteomics, many 
      additional classes of ZFs were identified based upon their primary amino acid 
      sequences. At least 13 additional classes of ZFs are known, and collectively 
      these "nonclassical" ZFs differ in the ligand set involved in Zn(II) 
      coordination, the organization of the ligands within the polypeptide sequence and 
      the macromolecular targets. Some nonclassical ZFs are DNA binding "transcription 
      factors", while others are involved in RNA regulation and protein recognition. 
      Much less is known about these nonclassical ZFs with regards to the roles of 
      metal coordination in fold and function. This Account focuses on our laboratory's 
      efforts to characterize two families of "nonclassical" ZFs: the Cys3His (or CCCH) 
      ZF family and the Cys2His2Cys (or CCHHC) ZF family. Our work on the CCCH ZF 
      family has focused on the protein Tristetraprolin (TTP), which is a key protein 
      in regulating inflammation. TTP contains two CCCH domains that were proposed to 
      be ZFs based upon their sequence. We have shown that while this protein can 
      coordinate Zn(II) at the CCCH sites, it can also coordinate Fe(II) and Fe(III). 
      Moreover, the zinc and iron bound forms of TTP are equally adept at 
      discriminating between RNA targets, which we have demonstrated via a fluorescence 
      anisotropy based approach. Thus, CCCH type ZFs appear to be promiscuous with 
      respect to metal preference and a role for iron coordination in CCCH ZF function 
      is proposed. The CCHHC family of ZFs is a small family of nonclassical ZFs that 
      are essential for the development of the central nervous system. There are three 
      ZFs in this family: neural zinc finger factor-1 (NZF-1), myelin transcription 
      factor-1 (MyT1), and suppressor of tumorgenicity 18 (ST18). All three proteins 
      contain multiple clusters of "CCHHC" domains, which are all predicted to be Zn 
      binding domains. We have focused on a tandem-CCHHC domain construct of NZF-1, 
      which recognizes beta-RARE DNA, and we have identified key residues required for DNA 
      recognition. Unlike classical ZFs, for which a few conserved residues are 
      required for DNA recognition, the CCHHC class of ZFs utilize a few nonconserved 
      residues to drive DNA recognition leading us to propose a new paradigm for ZF/DNA 
      binding.
FAU - Lee, Seung Jae
AU  - Lee SJ
AD  - Department of Chemistry and Research Institute of Physics and Chemistry, Chonbuk 
      National University , Jeonju 561-756, Republic of Korea.
FAU - Michel, Sarah L J
AU  - Michel SL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140806
PL  - United States
TA  - Acc Chem Res
JT  - Accounts of chemical research
JID - 0157313
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ferric Compounds)
RN  - 0 (Metals)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - DNA/chemistry/metabolism
MH  - DNA-Binding Proteins/*chemistry/metabolism
MH  - Ferric Compounds/chemistry
MH  - Gene Expression Regulation
MH  - Metals/*chemistry/metabolism
MH  - Molecular Sequence Data
MH  - Oxidation-Reduction
MH  - Protein Binding
MH  - Repressor Proteins/*chemistry/metabolism
MH  - Trans-Activators/*chemistry/metabolism
MH  - Zinc Fingers
EDAT- 2014/08/08 06:00
MHDA- 2015/08/28 06:00
CRDT- 2014/08/08 06:00
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/08/28 06:00 [medline]
AID - 10.1021/ar500182d [doi]
PST - ppublish
SO  - Acc Chem Res. 2014 Aug 19;47(8):2643-50. doi: 10.1021/ar500182d. Epub 2014 Aug 6.