@article{ce584be785744b0c940d2f3bba53940d,
title = "The pilus usher controls protein interactions via domain masking and is functional as an oligomer",
abstract = "The chaperone-usher (CU) pathway assembles organelles termed pili or fimbriae in Gram-negative bacteria. Type 1 pili expressed by uropathogenic Escherichia coli are prototypical structures assembled by the CU pathway. Biogenesis of pili by the CU pathway requires a periplasmic chaperone and an outer-membrane protein termed the usher (FimD). We show that the FimD C-terminal domains provide the high-affinity substrate-binding site but that these domains are masked in the resting usher. Domain masking requires the FimD plug domain, which serves as a switch controlling usher activation. We demonstrate that usher molecules can act in trans for pilus biogenesis, providing conclusive evidence for a functional usher oligomer. These results reveal mechanisms by which molecular machines such as the usher regulate and harness protein-protein interactions and suggest that ushers may interact in a cooperative manner during pilus assembly in bacteria.",
author = "Werneburg, {Glenn T.} and Henderson, {Nadine S.} and Portnoy, {Erica B.} and Samema Sarowar and Hultgren, {Scott J.} and Huilin Li and Thanassi, {David G.}",
note = "Funding Information: We thank the Schultz laboratory (Scripps Research Institute) for providing plasmid pEVOL-pBpF. We thank S. Van Horn of the Stony Brook University Central Microscopy Imaging Center and V. Sampath (Stony Brook University) for assistance with EM. We thank J. Haley, D. Martin and R. Rieger of the Stony Brook Proteomics Center for performing the mass spectrometry analysis and for helpful discussions. We thank S. Scarlata (Stony Brook University), A.W. Karzai (Stony Brook University), K.W. Dodson (Washington University) and A.H. Delcour (University of Houston) for helpful discussions and critical reading of the manuscript. This study was supported by US National Institutes of Health (NIH) grants R01GM062987 (to D.G.T. and H.L.) and R01AI029549 (to S.J.H.). G.T.W. was supported by Medical Scientist Training Program award T32GM008444 and National Research Service Award F30AI112252 from the NIH. The Stony Brook Proteomics Center receives support from NIH award S10RR023680. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc. All rights reserved.",
year = "2015",
month = jul,
day = "9",
doi = "10.1038/nsmb.3044",
language = "English",
volume = "22",
pages = "540--546",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
number = "7",
}