title: The leucine-rich repeat domain of Internalin B folds along a polarized N-terminal pathway.
abstract: The leucine-rich repeat domain of Internalin B is composed of seven tandem leucine-rich repeats, which each contain a short beta strand connected to a 3(10) helix by a short turn, and an N-terminal alpha-helical capping motif. To determine whether folding proceeds along a single, discrete pathway or multiple, parallel pathways, and to map the structure of the transition state ensemble, we examined the effects of destabilizing substitutions of conserved residues in each repeat. We find that, despite the structural redundancy among the repeats, folding proceeds through an N-terminal transition state ensemble in which the extent of structure formation is biased toward repeats one and two and includes both local and interrepeat interactions. Our results suggest that the N-terminal capping motif serves to polarize the folding pathway by acting as a fast-growing nucleus onto which consecutive repeats fold in the transition state ensemble, and highlight the importance of sequence-specific interactions in pathway selection.
authors.affiliation: T.C. Jenkins Department of Biophysics, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Courtemanche
authors.forename: Doug
authors.initials: D
authors.lastname: Barrick
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D014644:Genetic Variation; D007700:Kinetics; D007930:Leucine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D014508:Urea; D007930:Leucine