Titin; a multidomain protein that behaves as the sum of its parts.
Titin is a giant, multidomain muscle protein forming a major component of the sarcomere in vertebrate striated muscle. As for many other multidomain proteins, the properties of titin are often studied by characterisation of the constituent domains in isolation. This raises the question of to what extent the properties of the isolated domains are representative of the domains in the wild-type protein. We address this question for the I-band region of titin, which is of particular biological interest due to its role in muscle elasticity, by determining the properties of five immunoglobulin domains from the I-band in three different contexts; firstly as isolated domains with the boundaries defined conservatively, secondly, with a two amino acid extension at both the N and C terminus and thirdly as part of multidomain constructs. We show that adjacent domains in the titin I-band have very different kinetic properties which, in general, undergo only a small change in the presence of neighbouring domains and conclude that, provided that care is taken in the choice of domain boundaries, the properties of the titin I-band are essentially "the sum of its parts". From this and other work we propose that variation in kinetic properties between adjacent domains may be a general property of the I-band thereby preventing misfolding events on muscle relaxation.
Scott
Kathryn A
KA
MRC Centre for Protein Engineering, University of Cambridge Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK.
Steward
Annette
A
Fowler
Susan B
SB
Clarke
Jane
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D064211:Connectin; D004220:Disulfides / Q000378:metabolism; D015195:Drug Design; D004548:Elasticity; D005453:Fluorescence; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D007700:Kinetics; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry; D011489:Protein Denaturation / Q000187:drug effects; D015202:Protein Engineering; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D020673:Protein Renaturation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D064211:Connectin; D004220:Disulfides; D007136:Immunoglobulins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases; D019791:Guanidine