title: The Ig doublet Z1Z2: a model system for the hybrid analysis of conformational dynamics in Ig tandems from titin.
abstract: 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.
authors.affiliation: Division of Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Marino
authors.forename: Peijian
authors.initials: P
authors.lastname: Zou
authors.forename: Dmitri
authors.initials: D
authors.lastname: Svergun
authors.forename: Pilar
authors.initials: P
authors.lastname: Garcia
authors.forename: Christian
authors.initials: C
authors.lastname: Edlich
authors.forename: Bernd
authors.initials: B
authors.lastname: Simon
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
authors.forename: Claudia
authors.initials: C
authors.lastname: Muhle-Goll
authors.forename: Olga
authors.initials: O
authors.lastname: Mayans
mesh_terms: 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
chemical_list: D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases