Structural basis for nucleotide-dependent regulation of membrane-associated guanylate kinase-like domains.
CASK is a member of the membrane-associated guanylate kinases (MAGUK) homologs, a family of proteins that scaffold protein complexes at particular regions of the plasma membrane by utilizing multiple protein-binding domains. The GK domain of MAGUKs, which shares high similarity in amino acid sequence with yeast guanylate kinase (yGMPK), is the least characterized MAGUK domain both in structure and function. In addition to its scaffolding function, the GK domain of hCASK has been shown to be involved in transcription regulation. Here we report the crystal structure of the GK domain of human CASK (hCASK-GK) at 1.3-A resolution. The structure rationalizes the inability of the GK domain to catalyze phosphoryl transfer and strongly supports its new function as a protein-binding module. Comparison of the hCASK-GK structure with the available crystal structures of yGMPK provides insight into possible conformational changes that occur in hCASK upon GMP binding. These conformational changes may act to regulate hCASK-GK function in a nucleotide-dependent manner.
Li
Yuanhe
Y
Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, 60607, USA.
Spangenberg
Oliver
O
Paarmann
Ingo
I
Konrad
Manfred
M
Lavie
Arnon
A
D000595:Amino Acid Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018360:Crystallography, X-Ray; D006157:Guanosine Monophosphate / Q000378:metabolism / Q000502:physiology*; D051528:Guanylate Kinases; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D011994:Recombinant Proteins; D006157:Guanosine Monophosphate; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases