2QND

Crystal Structure of the KH1-KH2 domains from human Fragile X Mental Retardation Protein

Summary for 2QND

• Entry DOI: 10.2210/pdb2qnd/pdb
• Descriptor: FMR1 protein, MAGNESIUM ION (3 entities in total)
• Functional Keywords: kh domain, eukaryotic kh domains, tandem kh domains, type i kh domains, fragile x mental retardation protein, fmrp, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 32328.42

Authors

Valverde, R.,Regan, L. (deposition date: 2007-07-18, release date: 2007-11-06, Last modification date: 2024-10-30)

Primary citation

Valverde, R.,Pozdnyakova, I.,Kajander, T.,Venkatraman, J.,Regan, L.
Fragile X mental retardation syndrome: structure of the KH1-KH2 domains of fragile X mental retardation protein.
Structure, 15:1090-1098, 2007

PubMed Abstract: Fragile X syndrome is the most common form of inherited mental retardation in humans, with an estimated prevalence of about 1 in 4000 males. Although several observations indicate that the absence of functional Fragile X Mental Retardation Protein (FMRP) is the underlying basis of Fragile X syndrome, the structure and function of FMRP are currently unknown. Here, we present an X-ray crystal structure of the tandem KH domains of human FMRP, which reveals the relative orientation of the KH1 and KH2 domains and the location of residue Ile304, whose mutation to Asn is associated with a particularly severe incidence of Fragile X syndrome. We show that the Ile304Asn mutation both perturbs the structure and destabilizes the protein.

PubMed: 17850748
DOI: 10.1016/j.str.2007.06.022

Experimental method

X-RAY DIFFRACTION (1.9 Å)