title: Solution structure of ZASP PDZ domain; implications for sarcomere ultrastructure and enigma family redundancy.
abstract: Z band alternately spliced PDZ-containing protein (ZASP) is a sarcomere Z disk protein expressed in human cardiac and skeletal muscle that is thought to be involved in a dominant familial dilated cardiomyopathy. The N-terminal PDZ domain of ZASP interacts with the C terminus of alpha-actinin-2, the major component of the Z disk, probably by forming a ternary complex with titin Z repeats. We have determined the structure of ZASP PDZ by NMR and showed that it is a classical class 1 PDZ domain that recognizes the carboxy-terminal sequence of an alpha-actinin-2 calmodulin-like domain with micromolar affinity. We also characterized the role of each component in the ternary complex ZASP/alpha-actinin-2/titin, showing that the alpha-actinin-2/ZASP PDZ interaction involves a binding surface distinct from that recognized by the titin Z repeats. ZASP PDZ structure was used to model other members of the enigma family by homology and to predict their abilities to bind alpha-actinin-2.
authors.affiliation: National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.
authors.forename: Yunghan
authors.initials: Y
authors.lastname: Au
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Atkinson
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Geoff
authors.initials: G
authors.lastname: Kelly
authors.forename: Catherine
authors.initials: C
authors.lastname: Joseph
authors.forename: Steven R
authors.initials: SR
authors.lastname: Martin
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Muskett
authors.forename: Alberto
authors.initials: A
authors.lastname: Pallavicini
authors.forename: Georgine
authors.initials: G
authors.lastname: Faulkner
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000185:Actinin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D064211:Connectin; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009124:Muscle Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012518:Sarcomeres / Q000737:chemistry* / Q000378:metabolism
chemical_list: C401401:ACTN2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D064211:Connectin; D018398:Homeodomain Proteins; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; D009124:Muscle Proteins; C577285:TTN protein, human; D000185:Actinin; D011494:Protein Kinases