The Leucine-Rich Repeat Domain of Internalin B Folds along a Polarized N-Terminal Pathway

Naomi Courtemanche, Doug Barrick

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The leucine-rich repeat domain of Internalin B is composed of seven tandem leucine-rich repeats, which each contain a short β strand connected to a 310 helix by a short turn, and an N-terminal α-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.

Original languageEnglish (US)
Pages (from-to)705-714
Number of pages10
JournalStructure
Volume16
Issue number5
DOIs
StatePublished - May 7 2008

Bibliographical note

Funding Information:
We thank Partho Ghosh and Pascale Cossart for providing us with the InlB clone, and Thomas Kiefhaber and Andreas Moeglich for providing scripts for multistate fitting. This work was supported by National Institutes of Health grant GM68462, awarded to D.B.

Keywords

  • PROTEINS

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