title: Evidence for a dimeric assembly of two titin/telethonin complexes induced by the telethonin C-terminus.
abstract: The Z-disk region defines the lateral boundary of the sarcomere and requires a high level of mechanical strength to provide a stable framework for large filamentous muscle proteins. The level of complexity at this area is reflected by a large number of protein-protein interactions. Recently, we unraveled how the N-terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the N-terminal titin-binding segment of the Z-disk ligand telethonin/T-cap [Zou, P., Pinotsis, N., Lange, S., Song, Y.H., Popov, A., Mavridis, I., Mayans, O.M., Gautel, M., Wilmanns, M., 2006. Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk. Nature 439, 229-233]. In this contribution, we present structural data of a related complex of the titin N-terminus with full-length telethonin. The C-terminus of telethonin remains invisible, suggesting that it does not fold into a defined structure even in the presence of titin. In contrast to the structure with truncated telethonin, a dimer of two titin/telethonin complexes is formed within the crystal environment, potentially indicating the formation of higher oligomers. We further investigated the structure and dynamics of this assembly by small-angle X-ray scattering, circular dichroism, and in vivo complementation data. The data consistently indicate the involvement of the C-terminal part of telethonin into the assembly of two titin/telethonin complexes.
authors.affiliation: EMBL-Hamburg, c/o DESY, Notkeststrasse 85, D-22603 Hamburg, Germany. pinotsis@embl-hamburg.de
authors.forename: Nikos
authors.initials: N
authors.lastname: Pinotsis
authors.forename: Maxim
authors.initials: M
authors.lastname: Petoukhov
authors.forename: Stephan
authors.initials: S
authors.lastname: Lange
authors.forename: Dmitri
authors.initials: D
authors.lastname: Svergun
authors.forename: Peijian
authors.initials: P
authors.lastname: Zou
authors.forename: Mathias
authors.initials: M
authors.lastname: Gautel
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002942:Circular Dichroism / Q000379:methods; D064211:Connectin; D003460:Crystallization / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D005816:Genetic Complementation Test; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal / Q000379:methods; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D012518:Sarcomeres / Q000378:metabolism
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D010446:Peptide Fragments; C577292:TCAP protein, human; C577285:TTN protein, human; D011494:Protein Kinases