Solution scattering suggests cross-linking function of telethonin in the complex with titin.
Telethonin interacts specifically with the two Z-disk IG-like domains (Z1Z2) at the N terminus of titin, the largest presently known protein. Analytical ultracentrifugation and synchrotron radiation x-ray scattering were employed to study the solution structures of Z1Z2 and its complexes with telethonin, and low resolution models were constructed ab initio from the scattering data. A seven residues-long polyhistidine tag was localized at the tip of the Z1 domain by comparison of independent models of native and His-tagged versions of Z1Z2. The stoichiometry and shape of the complex between the telethonin construct lacking the C terminus and Z1Z2 indicate antiparallel association of two Z1Z2 molecules with telethonin acting as a central linker. The complex of full-length telethonin with Z1Z2 appears to also have a 1:2 stoichiometry at concentrations below 1 mg/ml but dimerizes at higher concentrations. These results suggest a possible role of telethonin in linking titin filaments at the Z-disk periphery.
Zou
Peijian
P
European Molecular Biology Laboratory (EMBL), Hamburg Outstation, EMBL c/o Deutsches Electronen- Synchrotron (DESY), Notkestrasse 85, Germany.
Gautel
Mathias
M
Geerlof
Arie
A
Wilmanns
Matthias
M
Koch
Michel H J
MH
Svergun
Dmitri I
DI
D003001:Cloning, Molecular; D064211:Connectin; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015233:Models, Statistical; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D013223:Statistics as Topic; D017356:Synchrotrons; D020798:Two-Hybrid System Techniques; D014461:Ultracentrifugation; D014965:X-Rays
D064211:Connectin; D009124:Muscle Proteins; C577292:TCAP protein, human; C577285:TTN protein, human; D011494:Protein Kinases