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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Asparagine / genetics
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Binding Sites / physiology
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Carrier Proteins*
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Fragile X Syndrome / genetics
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Fragile X Syndrome / metabolism*
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Humans
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Isoleucine / genetics
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Magnetic Resonance Spectroscopy
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Molecular Sequence Data
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Mutagenesis / physiology
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Mutagenesis, Site-Directed
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Phenotype
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Protein Conformation
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Protein Structure, Tertiary
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Proteins / chemistry
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RNA-Binding Proteins / chemistry*
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Sequence Homology, Amino Acid
Substances
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Carrier Proteins
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Proteins
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RNA-Binding Proteins
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Isoleucine
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high density lipoprotein binding protein
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Asparagine
Associated data
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GENBANK/D26120
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GENBANK/J02638
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GENBANK/J03453
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GENBANK/L25598
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GENBANK/M31304
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GENBANK/M64098
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GENBANK/M88108
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GENBANK/M91593
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GENBANK/S65791
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GENBANK/S74678
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GENBANK/S75665
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GENBANK/U04840
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GENBANK/U05040
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GENBANK/U10438
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GENBANK/U15928
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GENBANK/U19858
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GENBANK/U23177
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GENBANK/U25165
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GENBANK/U31501
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GENBANK/X75947
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GENBANK/X77291
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GENBANK/Z36101