Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition.
PDZ domain containing proteins assist formation of cell-cell junctions and localization of membrane protein receptors and ion channels. PDZ domains interact with the C-terminal residues of a particular target membrane protein. Based on their binding specificities and sequence homologies, PDZ domains fall into two classes. The first crystal structure of a class II PDZ domain, that of hCASK, has been solved by multi-wavelength anomalous dispersion phasing. Complex formation with the C-terminus of a neighboring non-crystallographically related PDZ domain reveals interactions between hCASK and its ligand. Class II PDZ domains differ from class I domains by formation of a second hydrophobic binding pocket. The C-terminal carboxylate binding loop of the PDZ domain is structurally conserved in both classes suggesting a generalized carboxylate binding motif (h-Gly-h) where h is a hydrophobic residue.
Daniels
D L
DL
The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Cohen
A R
AR
Anderson
J M
JM
Brünger
A T
AT
D000595:Amino Acid Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins; D051528:Guanylate Kinases; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; C092747:cno protein, Drosophila; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases