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Atomic model of human Rcd‐1 reveals an armadillo ‐like‐repeat protein with in vitro nucleic acid binding properties
Author(s) -
Garces Robert G.,
Gillon Wanda,
Pai Emil F.
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062600507
Subject(s) - nucleic acid , biology , armadillo , transcription factor , yeast , dna binding protein , microbiology and biotechnology , biochemistry , saccharomyces cerevisiae , rna recognition motif , genetics , rna binding protein , rna , gene
Rcd‐1, a protein highly conserved across eukaryotes, was initially identified as a factor essential for nitrogen starvation‐invoked differentiation in fission yeast, and its Saccharomyces cerevisiae homolog, CAF40, has been identified as part of the CCR4–NOT transcription complex, where it interacts with the NOT1 protein. Mammalian homologs are involved in various cellular differentiation processes including retinoic acid‐induced differentiation and hematopoetic cell development. Here, we present the 2.2 Å X‐ray structure of the highly conserved region of human Rcd‐1 and investigate possible functional abilities of this and the full‐length protein. The monomer is made up of six armadillo repeats forming a solvent‐accessible, positively‐charged cleft 21–22 Å wide that, in contrast to other armadillo proteins, stays fully exposed in the dimer. Prompted by this finding, we established that Rcd‐1 can bind to single‐ and double‐stranded oligonucleotides in vitro with the affinity of G/C/T ≫ A. Mutation of an arginine residue within the cleft strongly reduced or abolished oligonucleotide binding. Rcd‐1's ability to bind to nucleic acids, in addition to the previously reported protein–protein interaction with NOT1, suggests a new feature in Rcd‐1's role in regulation of overall cellular differentiation processes.