When a module is also a domain: the role of the N terminus in the stability and the dynamics of immunoglobulin domains from titin
Φόρτωση...
Ημερομηνία
Συγγραφείς
Pfuhl, M.
Improta, S.
Politou, A. S.
Pastore, A.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
J Mol Biol
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
In the course of a structural study of titin, a giant modular protein from muscle, we have reported that N-terminal extension of immunoglobulin-like (Ig-like) domains from titin stabilizes this fold. In order to investigate the structural basis of such an effect, we have solved the structure of NEXTM5, which has six amino acids added to the sequence of M5, a domain for which full structure determination has been previously achieved. In the present work, the structures and the dynamics of M5 and NEXTM5 are compared in the light of data collected for these and other titin domains. In NEXTM5, three out of the six added residues are structured and pack against the nearby BC and FG loops. As a consequence, three new backbone hydrogen bonds are formed with the B strand, extending the A strand by two residues and decreasing the exposed surface area of the loops. Additional contacts which involve the side-chains give rise to a remarkable pH dependence of the stability. Interestingly, no correlation is observed on the NMR time-scale between the overall dynamics of the extended domain and its increased stability. The most noticeable differences between the two constructs are localised around the N terminus, which becomes more rigid upon extension. Since a similar pattern of contacts is observed for other domains of the immunoglobulin I-set, our results are of general relevance for this protein family. Our work might also inspire a more rational approach to the investigation of domain boundaries and their influence on module stability.
Περιγραφή
Λέξεις-κλειδιά
Algorithms, Amino Acid Sequence, Computer Simulation, Hydrogen Bonding, Immunoglobulins/*chemistry, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Muscle Proteins/*chemistry, *Protein Conformation, Protein Folding, Protein Kinases/*chemistry, Protein Structure, Secondary, Protein Structure, Tertiary, Protons, Thermodynamics
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/9020985
http://ac.els-cdn.com/S0022283696907251/1-s2.0-S0022283696907251-main.pdf?_tid=6dc7a25d43a47b5703979f53b594eb14&acdnat=1333006301_672de0691fcb5cf12db62d8686a67f7e
http://ac.els-cdn.com/S0022283696907251/1-s2.0-S0022283696907251-main.pdf?_tid=6dc7a25d43a47b5703979f53b594eb14&acdnat=1333006301_672de0691fcb5cf12db62d8686a67f7e
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής