The Ig doublet Z1Z2: a model system for the hybrid analysis of conformational dynamics in Ig tandems from titin.
Titin is a gigantic elastic filament that determines sarcomere ultrastructure and stretch response in vertebrate muscle. It folds into numerous Ig and FnIII domains connected in tandem. Data on interdomain arrangements and dynamics are essential for understanding the function of this filament. Here, we report a mechanistic analysis of the conformational dynamics of two Ig domains from the N terminus of titin, Z1Z2, by using X-ray crystallography, SAXS, NMR relaxation data, and residual dipolar couplings in combination. Z1Z2 preferentially adopts semiextended conformations in solution, with close-hinge arrangements representing low-probability states. Although interdomain contacts are not observed, the linker appears to acquire moderate rigidity via small, local hydrophobic interactions. Thus, Z1Z2 constitutes an adaptable modular system with restricted dynamics. We speculate that its preexistent conformation contributes to the selective recruitment of the binding partner telethonin onto the repetitive surface of the filament. The structural interconversion of four Z1Z2 conformers is analyzed.
Marino
Marco
M
Division of Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Zou
Peijian
P
Svergun
Dmitri
D
Garcia
Pilar
P
Edlich
Christian
C
Simon
Bernd
B
Wilmanns
Matthias
M
Muhle-Goll
Claudia
C
Mayans
Olga
O
D064211:Connectin; D018360:Crystallography, X-Ray; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008958:Models, Molecular; D009124:Muscle Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods
D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases