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RUN-CBFbeta interaction in C. elegans: computational prediction and experimental verification.

Abstract The Runt domain proteins are eukaryotic transcription factors that regulate major developmental pathways. All members of this family contain a highly-conserved sequence-specific DNA binding domain: the Runt domain (RD). Structural and biochemical studies have shown that the Runt domain undergoes a conformational transition upon binding to DNA and that this process is regulated by an unrelated partner protein CBFbeta that enhances the DNA binding affinity of RD. Most of the reported studies on the Runt domain transcription factors were performed on proteins from mammals and Drosophila whereas very little has been known about the C. elegans RD protein, RUN, which provides the simplest model system for understanding the function of this class of transcription factors. We performed computational studies on RD domains from various species including C. elegans, Drosophila, and human, using the atom-atom contact surface area scoring method. The scoring analysis indicates that the DNA binding regulation of the C. elegans RD protein (CeRD) occurs via its interaction with a CBFbeta-like partner, as found for the human proteins, whereas a different mode of regulation may occur in the Drosophila system. Sequence, secondary structure and fold analyses of a putative CBFbeta protein identified in the C. elegans genome, CeCBFbeta, sharing a 22% identity with the human protein, predict a similar structure of this protein to that of the human CBFbeta protein. We produced the C. elegans proteins CeRD and CeCBFbeta in bacteria and confirmed their physical interaction as well as cross interactions with the corresponding human proteins. We also confirmed the structural similarity of CBFbeta and CeCBFbeta by circular dichroism analysis. The combined results suggest that a similar mechanism of regulation operates for the human and the C. elegans RD proteins despite the low sequence identity between their CBFbeta proteins and the evolutionary distance between the two systems.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title journal of biomolecular structure & dynamics
Publication Year Start




PMID- 17206850
OWN - NLM
STAT- MEDLINE
DA  - 20070108
DCOM- 20070424
LR  - 20070108
IS  - 0739-1102 (Print)
IS  - 0739-1102 (Linking)
VI  - 24
IP  - 4
DP  - 2007 Feb
TI  - RUN-CBFbeta interaction in C. elegans: computational prediction and experimental 
      verification.
PG  - 343-58
AB  - The Runt domain proteins are eukaryotic transcription factors that regulate major
      developmental pathways. All members of this family contain a highly-conserved
      sequence-specific DNA binding domain: the Runt domain (RD). Structural and
      biochemical studies have shown that the Runt domain undergoes a conformational
      transition upon binding to DNA and that this process is regulated by an unrelated
      partner protein CBFbeta that enhances the DNA binding affinity of RD. Most of the
      reported studies on the Runt domain transcription factors were performed on
      proteins from mammals and Drosophila whereas very little has been known about the
      C. elegans RD protein, RUN, which provides the simplest model system for
      understanding the function of this class of transcription factors. We performed
      computational studies on RD domains from various species including C. elegans,
      Drosophila, and human, using the atom-atom contact surface area scoring method.
      The scoring analysis indicates that the DNA binding regulation of the C. elegans 
      RD protein (CeRD) occurs via its interaction with a CBFbeta-like partner, as
      found for the human proteins, whereas a different mode of regulation may occur in
      the Drosophila system. Sequence, secondary structure and fold analyses of a
      putative CBFbeta protein identified in the C. elegans genome, CeCBFbeta, sharing 
      a 22% identity with the human protein, predict a similar structure of this
      protein to that of the human CBFbeta protein. We produced the C. elegans proteins
      CeRD and CeCBFbeta in bacteria and confirmed their physical interaction as well
      as cross interactions with the corresponding human proteins. We also confirmed
      the structural similarity of CBFbeta and CeCBFbeta by circular dichroism
      analysis. The combined results suggest that a similar mechanism of regulation
      operates for the human and the C. elegans RD proteins despite the low sequence
      identity between their CBFbeta proteins and the evolutionary distance between the
      two systems.
FAU - Suad, Oded
AU  - Suad O
AD  - Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100,
      Israel.
FAU - Eyal, Eran
AU  - Eyal E
FAU - Blumenzweig, Immanuel
AU  - Blumenzweig I
FAU - Kessler, Naama
AU  - Kessler N
FAU - Levanon, Ditsa
AU  - Levanon D
FAU - Groner, Yoram
AU  - Groner Y
FAU - Shakked, Zippora
AU  - Shakked Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Core Binding Factor alpha Subunits)
RN  - 0 (DNA, Complementary)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Caenorhabditis elegans/*genetics
MH  - Caenorhabditis elegans Proteins/chemistry/*genetics
MH  - Cloning, Molecular
MH  - Core Binding Factor alpha Subunits/chemistry/*genetics
MH  - DNA, Complementary/genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Protein Biosynthesis
MH  - Protein Conformation
MH  - Recombinant Proteins/chemistry
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
EDAT- 2007/01/09 09:00
MHDA- 2007/04/25 09:00
CRDT- 2007/01/09 09:00
AID - d=3028&c=4221&p=15482&do=detail [pii]
AID - 10.1080/07391102.2007.10507124 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2007 Feb;24(4):343-58.