The elastic I-band region of titin is assembled in a "modular" fashion by weakly interacting Ig-like domains

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Μικρογραφία εικόνας

Ημερομηνία

Συγγραφείς

Politou, A. S.
Gautel, M.
Improta, S.
Vangelista, L.
Pastore, A.

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peer-reviewed

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Όνομα περιοδικού

J Mol Biol

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Συμπληρωματικός/δευτερεύων τίτλος

Περιγραφή

The vertebrate striated muscle protein titin is thought to play a critical role in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of this molecule through dissection into units that are structurally and/or functionally relevant. To understand the assembly process of titin, and ultimately the molecular basis of its elastic behaviour, we studied the thermodynamic properties of module pairs, the smallest structural unit that includes a module-module interface. Thus, selected module pairs and their component single modules from the I-band part of the titin molecule were expressed in Escherichia coli and their heat-induced and denaturant-induced unfolding was investigated with a combination of techniques (circular dichroism, fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of single modules and pairs were determined from denaturation experiments. The module interface was also modelled on the basis of the sequence alignment of all approximately 40 immunoglobulin like modules from the I-band and the known structure of one of them. Our results show that all modules and module pairs examined are independently folded in solution. When covalently linked, although weakly interacting, they still behave as autonomous co-operative units upon unfolding. These observations lead us to suggest that folding of titin in vitro is a hierarchical event and that weak interactions between its adjacent modules must only partly account for its presumed elastic function.

Περιγραφή

Λέξεις-κλειδιά

Amino Acid Sequence, Animals, Base Sequence, Circular Dichroism, DNA Primers, Heating, Humans, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Muscle Proteins/*chemistry/drug effects/genetics/metabolism, Protein Binding, Protein Denaturation, Protein Folding, Protein Kinases/*chemistry/drug effects/genetics/metabolism, Rabbits, Spectrometry, Fluorescence, Urea/pharmacology

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Σύνδεσμος

http://www.ncbi.nlm.nih.gov/pubmed/8568900
http://ac.els-cdn.com/S0022283696900509/1-s2.0-S0022283696900509-main.pdf?_tid=63ad0b3efee0d84c1c1e501f73ed800e&acdnat=1333006324_6eab8ae7a85ba797f1af2761b904569c

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en

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Γενική Περιγραφή / Σχόλια

Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος

Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής

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