Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk.
The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin. The pseudosymmetric structure of telethonin mediates a unique palindromic arrangement of two titin filaments, a type of molecular assembly previously found only in protein-DNA complexes. We have confirmed its unique architecture in vivo by protein complementation assays, and in vitro by experiments using fluorescence resonance energy transfer. The model proposed may provide a molecular paradigm of how major sarcomeric filaments are crosslinked, anchored and aligned within complex cytoskeletal networks.
Zou
Peijian
P
EMBL-Hamburg c/o DESY, Notkeststrasse 85, D-22603 Hamburg, Germany.
Pinotsis
Nikos
N
Lange
Stephan
S
Song
Young-Hwa
YH
Popov
Alexander
A
Mavridis
Irene
I
Mayans
Olga M
OM
Gautel
Mathias
M
Wilmanns
Matthias
M
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D064211:Connectin; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D005816:Genetic Complementation Test; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012518:Sarcomeres / Q000737:chemistry* / Q000378:metabolism*
D064211:Connectin; D008024:Ligands; D046912:Multiprotein Complexes; D009124:Muscle Proteins; C507454:Tcap protein, rat; D011494:Protein Kinases