Abstract |
The KH module is a sequence motif found in a number of proteins that are known to be in close association with RNA. Experimental evidence suggests a direct involvement of KH in RNA binding. The human FMR1 protein, which has two KH domains, is associated with fragile X syndrome, the most common inherited cause of mental retardation. Here we present the three-dimensional solution structure of the KH module. The domain consists of a stable beta alpha alpha beta beta alpha fold. On the basis of our results, we suggest a potential surface for RNA binding centered on the loop between the first two helices. Substitution of a well-conserved hydrophobic residue located on the second helix destroys the KH fold; a mutation of this position in FMR1 leads to an aggravated fragile X phenotype.
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Authors | G Musco, G Stier, C Joseph, M A Castiglione Morelli, M Nilges, T J Gibson, A Pastore |
Journal | Cell
(Cell)
Vol. 85
Issue 2
Pg. 237-45
(Apr 19 1996)
ISSN: 0092-8674 [Print] United States |
PMID | 8612276
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carrier Proteins
- Proteins
- RNA-Binding Proteins
- Isoleucine
- high density lipoprotein binding protein
- Asparagine
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Topics |
- Asparagine
(genetics)
- Binding Sites
(physiology)
- Carrier Proteins
- Fragile X Syndrome
(genetics, metabolism)
- Humans
- Isoleucine
(genetics)
- Magnetic Resonance Spectroscopy
- Molecular Sequence Data
- Mutagenesis
(physiology)
- Mutagenesis, Site-Directed
- Phenotype
- Protein Conformation
- Protein Structure, Tertiary
- Proteins
(chemistry)
- RNA-Binding Proteins
(chemistry)
- Sequence Homology, Amino Acid
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