Molecular structure of the sarcomeric Z-disk: two types of titin interactions lead to an asymmetrical sorting of alpha-actinin.
The sarcomeric Z-disk, the anchoring plane of thin (actin) filaments, links titin (also called connectin) and actin filaments from opposing sarcomere halves in a lattice connected by alpha-actinin. We demonstrate by protein interaction analysis that two types of titin interactions are involved in the assembly of alpha-actinin into the Z-disk. Titin interacts via a single binding site with the two central spectrin-like repeats of the outermost pair of alpha-actinin molecules. In the central Z-disk, titin can interact with multiple alpha-actinin molecules via their C-terminal domains. These interactions allow the assembly of a ternary complex of titin, actin and alpha-actinin in vitro, and are expected to constrain the path of titin in the Z-disk. In thick skeletal muscle Z-disks, titin filaments cross over the Z-disk centre by approximately 30 nm, suggesting that their alpha-actinin-binding sites overlap in an antiparallel fashion. The combination of our biochemical and ultrastructural data now allows a molecular model of the sarcomeric Z-disk, where overlapping titin filaments and their interactions with the alpha-actinin rod and C-terminal domain can account for the essential ultrastructural features.
Young
P
P
European Molecular Biology Laboratory, Postfach 10 22 09, 69012 Heidelberg, Germany.
Ferguson
C
C
Bañuelos
S
S
Gautel
M
M
D008841:Actin Cytoskeleton / Q000378:metabolism; D000185:Actinin / Q000737:chemistry / Q000378:metabolism*; D000199:Actins / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D064211:Connectin; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D012518:Sarcomeres / Q000737:chemistry* / Q000378:metabolism; D013049:Spectrin
D000199:Actins; D064211:Connectin; D008024:Ligands; D009124:Muscle Proteins; C577285:TTN protein, human; C035620:nebulin; D000185:Actinin; D013049:Spectrin; D011494:Protein Kinases