PMID- 15491138
OWN - NLM
STAT- MEDLINE
DCOM- 20041202
LR  - 20131121
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 43
IP  - 42
DP  - 2004 Oct 26
TI  - Structural studies on a protein-binding zinc-finger domain of Eos reveal both 
      similarities and differences to classical zinc fingers.
PG  - 13318-27
AB  - The oligomerization domain that is present at the C terminus of Ikaros-family 
      proteins and the protein Trps-1 is important for the proper regulation of 
      developmental processes such as hematopoiesis. Remarkably, this domain is 
      predicted to contain two classical zinc fingers (ZnFs), domains normally 
      associated with the recognition of nucleic acids. The preference for protein 
      binding by these predicted ZnFs is not well-understood. We have used a range of 
      methods to gain insight into the structure of this domain. Circular dichroism, 
      UV-vis, and NMR experiments carried out on the C-terminal domain of Eos (EosC) 
      revealed that the two putative ZnFs (C1 and C2) are separable, i.e., capable of 
      folding independently in the presence of Zn(II). We next determined the structure 
      of EosC2 using NMR spectroscopy, revealing that, although the overall fold of 
      EosC2 is similar to other classical ZnFs, a number of differences exist. For 
      example, the conformation of the C terminus of EosC2 appears to be flexible and 
      may result in a major rearrangement of the zinc ligands. Finally, 
      alanine-scanning mutagenesis was used to identify the residues that are involved 
      in the homo- and hetero-oligomerization of Eos, and these results are discussed 
      in the context of the structure of EosC. These studies provide the first 
      structural insights into how EosC mediates protein-protein interactions and 
      contributes to our understanding of why it does not exhibit high-affinity DNA 
      binding.
FAU - Westman, Belinda J
AU  - Westman BJ
AD  - School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New 
      South Wales 2006, Australia.
FAU - Perdomo, Jose
AU  - Perdomo J
FAU - Matthews, Jacqueline M
AU  - Matthews JM
FAU - Crossley, Merlin
AU  - Crossley M
FAU - Mackay, Joel P
AU  - Mackay JP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IKZF1 protein, human)
RN  - 0 (IKZF5 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Isoforms)
RN  - 0 (Transcription Factors)
RN  - 0 (Xenopus Proteins)
RN  - 0 (Zfpn1a1 protein, mouse)
RN  - 0 (Zfpn1a4 protein, mouse)
RN  - 148971-36-2 (Ikaros Transcription Factor)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites/genetics
MH  - Carrier Proteins/*chemistry/genetics
MH  - DNA-Binding Proteins/*chemistry/genetics
MH  - Humans
MH  - Ikaros Transcription Factor
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nerve Tissue Proteins/*chemistry/genetics
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Peptide Fragments/*chemistry/genetics
MH  - Protein Binding/genetics
MH  - Protein Conformation
MH  - Protein Folding
MH  - Protein Isoforms/chemistry/genetics
MH  - Protein Structure, Tertiary/genetics
MH  - Static Electricity
MH  - Structural Homology, Protein
MH  - Transcription Factors/*chemistry/genetics
MH  - Xenopus Proteins/chemistry/genetics
MH  - Zinc/chemistry
MH  - *Zinc Fingers/genetics
EDAT- 2004/10/20 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/20 09:00
PHST- 2004/10/20 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/20 09:00 [entrez]
AID - 10.1021/bi049506a [doi]
PST - ppublish
SO  - Biochemistry. 2004 Oct 26;43(42):13318-27. doi: 10.1021/bi049506a.