A phosphorylation-induced conformation change in dematin headpiece.
Dematin is an actin binding protein from the junctional complex of the erythrocyte cytoskeleton. The protein has two actin binding sites and bundles actin filaments in vitro. This actin bundling activity is reversibly regulated by phosphorylation in the carboxyl terminal "headpiece" domain (DHP). DHP is a typical villin-type headpiece actin binding motif and contains a flexible N-terminal loop and an alpha-helical C-terminal subdomain that is phosphorylated at Ser74. The NMR structure of a Ser74-to-Glu mutant (DHPs74e) closely mimics the conformation of phosphorylated DHP. The negative charge at Ser74 does not alter the conformation of the C-terminal subdomain, but attracts the N-terminal loop toward the C terminus, changing the orientation of the N-terminal subdomain. NMR relaxation studies also indicate reduced mobility in the N-terminal loop in DHPs74e. Thus, phosphorylation in DHP serves as a switch controlling the conformational state of DHP and the actin bundling activity of dematin.
Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA.
Zhenghui Gordon
ZG
Jiang
C James
CJ
McKnight
D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009038:Motion; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary
D001798:Blood Proteins; C044805:DMTN protein, human; D008840:Microfilament Proteins; D010750:Phosphoproteins