The importance of loop length in the folding of an immunoglobulin domain.
Immunoglobulin (Ig)-like proteins have been shown to fold following formation of a nucleus comprising interactions between residues that are distant in the primary sequence. What role do the loops connecting these nucleus residues play? Here, the importance of loops connecting beta-strands in different sheets of the Ig fold is investigated, by insertion of five glycine residues into the B-C loop of an Ig domain from human titin, TI I27. The folding pathway of this elongated 'pseudo wild-type' TI I27 is probed using protein engineering and Phi-value analysis. The Phi-values calculated for mutants within the pseudo wild-type protein indicate that the folding nucleus in wild-type TI I27 is conserved, supporting the hypothesis that the inter-sheet loop is not critical to the formation of a long-range folding nucleus.
Wright
Caroline F
CF
University of Cambridge, Department of Chemistry, Lensfield Road, CB2 1EW, UK.
Christodoulou
John
J
Dobson
Christopher M
CM
Clarke
Jane
J
D000595:Amino Acid Sequence; D064211:Connectin; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases