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

@article{Courtemanche2008, abstract = {Summary 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 310 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.}, author = {Courtemanche, Naomi and Barrick, Doug }, citeulike-article-id = {2763417}, journal = {Structure}, keywords = {folding, leucine, lrr, pathway, protein, repeat}, month = {May}, pages = {705--714}, posted-at = {2008-05-07 02:37:18}, priority = {2}, title = {The Leucine-Rich Repeat Domain of Internalin B Folds along a Polarized N-Terminal Pathway}, url = {http://www.sciencedirect.com/science/article/B6VSR-4SFHFDJ-C/1/c6b26638756159a6c2a369f1ee460690}, volume = {16}, year = {2008} }

TY - JOUR ID - Courtemanche2008 L3 - citeulike-article-id:2763417 TI - The Leucine-Rich Repeat Domain of Internalin B Folds along a Polarized N-Terminal Pathway JF - Structure VL - 16 SP - 705 EP - 714 N2 - Summary 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 310 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. KW - folding KW - leucine KW - lrr KW - pathway KW - protein KW - repeat AU - Courtemanche, Naomi AU - Barrick, Doug PY - 2008/May// UR - http://www.sciencedirect.com/science/article/B6VSR-4SFHFDJ-C/1/c6b26638756159a6c2a369f1ee460690 ER -