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Structural investigations of the p53/p73 homologs from the tunicate species Ciona intestinalis reveal the sequence requirements for the formation of a tetramerization domain.


ABSTRACT: Most members of the p53 family of transcription factors form tetramers. Responsible for determining the oligomeric state is a short oligomerization domain consisting of one ?-strand and one ?-helix. With the exception of human p53 all other family members investigated so far contain a second ?-helix as part of their tetramerization domain. Here we have used nuclear magnetic resonance spectroscopy to characterize the oligomerization domains of the two p53-like proteins from the tunicate Ciona intestinalis, representing the closest living relative of vertebrates. Structure determination reveals for one of the two proteins a new type of packing of this second ?-helix on the core domain that was not predicted based on the sequence, while the other protein does not form a second helix despite the presence of crucial residues that are conserved in all other family members that form a second helix. By mutational analysis, we identify a proline as well as large hydrophobic residues in the hinge region between both helices as the crucial determinant for the formation of a second helix.

SUBMITTER: Heering J 

PROVIDER: S-EPMC4815341 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Structural investigations of the p53/p73 homologs from the tunicate species Ciona intestinalis reveal the sequence requirements for the formation of a tetramerization domain.

Heering Jan J   Jonker Hendrik R A HR   Löhr Frank F   Schwalbe Harald H   Dötsch Volker V  

Protein science : a publication of the Protein Society 20151125 2


Most members of the p53 family of transcription factors form tetramers. Responsible for determining the oligomeric state is a short oligomerization domain consisting of one β-strand and one α-helix. With the exception of human p53 all other family members investigated so far contain a second α-helix as part of their tetramerization domain. Here we have used nuclear magnetic resonance spectroscopy to characterize the oligomerization domains of the two p53-like proteins from the tunicate Ciona int  ...[more]

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