When a module is also a domain: the role of the N terminus in the stability and the dynamics of immunoglobulin domains from titin (Journal article)

Pfuhl, M./ Improta, S./ Politou, A. S./ Pastore, A.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: 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
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/21387
ISSN: 0022-2836
Link: 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
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

Files in This Item:
File Description SizeFormat 
Pfuhl-1997-When a module is als.pdf1.5 MBAdobe PDFView/Open    Request a copy


 Please use this identifier to cite or link to this item:
https://olympias.lib.uoi.gr/jspui/handle/123456789/21387
  This item is a favorite for 0 people.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.