Fragile X Mental Retardation Syndrome: Structure of the KH1-KH2 Domains of Fragile X Mental Retardation Protein

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Structure

DOI:https://doi.org/10.1016/j.str.2007.06.022· OSTI ID:929959

Valverde, R; Poznyakova, I; Kajander, T; Venkatraman, J; Regan, L

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 929959
• Report Number(s): BNL--80561-2008-JA
• Journal Information: Structure, Journal Name: Structure Vol. 15
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
FUNCTIONS
GENETICS
HANDICAPPED PEOPLE
HEREDITARY DISEASES
HUMAN POPULATIONS
MALES
MUTATIONS
ORIENTATION
PROTEINS
RESIDUES
national synchrotron light source