Structure of the pleckstrin homology domain from beta-spectrin.
The 'pleckstrin homology' or PH domain is a 100-residue protein module. It is present in many kinases, different isoforms of phospholipase C, GTPase-activating proteins and nucleotide-exchange factors. Its function is not known, but many proteins that contain a PH domain interact with GTP-binding proteins. The PH domain in beta-adrenergic receptor kinase may be involved in binding to the beta gamma subunits of a trimeric G-protein. We report here the three-dimensional structure of the PH domain of the cytoskeletal protein spectrin using homonuclear nuclear magnetic resonance. The core of the molecule is an antiparallel beta-sheet consisting of seven strands. The C terminus is folded into a long alpha-helix, and another helix is present in one of the surface loops. The molecule is electrostatically polarized and contains a pocket which may be involved in the binding of a ligand. There is a distant relationship to the peptidyl-prolyl-cis-trans-isomerase FKBP in which this pocket is involved in the binding of the macrocyclic compound FK506 (refs 8-11).
Macias
M J
MJ
European Molecular Biology Laboratory, Heidelberg, Germany.
Musacchio
A
A
Ponstingl
H
H
Nilges
M
M
Saraste
M
M
Oschkinat
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D003196:Computer Graphics; D004563:Electrochemistry; D004926:Escherichia coli; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry*
D001798:Blood Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C039077:platelet protein P47; D013049:Spectrin