TY - JOUR
T1 - The structure of the N-terminal domain of the fragile X mental retardation protein
T2 - A platform for protein-protein interaction
AU - Ramos, Andres
AU - Hollingworth, David
AU - Adinolfi, Salvatore
AU - Castets, Marie
AU - Kelly, Geoff
AU - Frenkiel, Thomas A.
AU - Bardoni, Barbara
AU - Pastore, Annalisa
N1 - Funding Information:
The work was supported by a Human Frontiers Science Program grant. B.B. also acknowledges financial support from CNRS and from the French Fondation pour la Recherche Médical.
PY - 2006/1
Y1 - 2006/1
N2 - FMRP, whose lack of expression causes the X-linked fragile X syndrome, is a modular RNA binding protein thought to be involved in posttranslational regulation. We have solved the structure in solution of the N-terminal domain of FMRP (NDF), a functionally important region involved in multiple interactions. The structure consists of a composite fold comprising two repeats of a Tudor motif followed by a short α helix. The interactions between the three structural elements are essential for the stability of the NDF fold. Although structurally similar, the two repeats have different dynamic and functional properties. The second, more flexible repeat is responsible for interacting both with methylated lysine and with 82-FIP, one of the FMRP nuclear partners. NDF contains a 3D nucleolar localization signal, since destabilization of its fold leads to altered nucleolar localization of FMRP. We suggest that the NDF composite fold determines an allosteric mechanism that regulates the FMRP functions.
AB - FMRP, whose lack of expression causes the X-linked fragile X syndrome, is a modular RNA binding protein thought to be involved in posttranslational regulation. We have solved the structure in solution of the N-terminal domain of FMRP (NDF), a functionally important region involved in multiple interactions. The structure consists of a composite fold comprising two repeats of a Tudor motif followed by a short α helix. The interactions between the three structural elements are essential for the stability of the NDF fold. Although structurally similar, the two repeats have different dynamic and functional properties. The second, more flexible repeat is responsible for interacting both with methylated lysine and with 82-FIP, one of the FMRP nuclear partners. NDF contains a 3D nucleolar localization signal, since destabilization of its fold leads to altered nucleolar localization of FMRP. We suggest that the NDF composite fold determines an allosteric mechanism that regulates the FMRP functions.
UR - http://www.scopus.com/inward/record.url?scp=33644799748&partnerID=8YFLogxK
U2 - 10.1016/j.str.2005.09.018
DO - 10.1016/j.str.2005.09.018
M3 - Article
C2 - 16407062
AN - SCOPUS:33644799748
SN - 0969-2126
VL - 14
SP - 21
EP - 31
JO - Structure
JF - Structure
IS - 1
ER -