Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11261-6. Epub 2003 Sep 18.

NMR structure of the forkhead-associated domain from the Arabidopsis receptor kinase-associated protein phosphatase.

Author information

1
Department of Biochemistry, 117 Schweitzer Hall, and Division of Biological Sciences, 105 Tucker Hall, University of Missouri, Columbia, MO 65211, USA.

Abstract

Forkhead-associated (FHA) domains are phosphoprotein-binding modules found in diverse signaling proteins that bind partners phosphorylated on threonine or serine. Kinase-associated protein phosphatase from Arabidopsis employs its FHA domain for negative regulation of receptor-like kinase signaling pathways, which are important in plant development. The solution structure of the free state of kinase-interacting FHA domain (KI-FHA) of kinase-associated protein phosphatase has been determined with high precision and accuracy using residual dipolar couplings. KI-FHA is a sandwich of a five-stranded mixed beta-sheet with a six-stranded antiparallel beta-sheet. Despite homology only in the recognition loops, this fold is shared with FHA domains from checkpoint proteins from yeast and humans, as well as with nonhomologous MH2 domains of Smad tumor suppressors. A shared pattern of hydrophobicity throughout FHA domains and Smad MH2 domains may stabilize the core of the beta-sandwich. Evolutionary trace analysis of FHA domains suggests class-specific residues in the recognition loops that could tune their phosphoprotein-binding specificity. This surface agrees with that of KI-FHA in contact with a phosphothreonine peptide ligand. Evolutionary trace analysis also predicts an unexpected swath of class-specific residues on another face of FHA domains. Protein interactions with these faces may affect assembly of transmembrane signaling complexes in plants, and in other FHA domain-containing assemblies.

PMID:
14500786
PMCID:
PMC208745
DOI:
10.1073/pnas.2031918100
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center