Structural Determinants of Polymerization Reactivity of the P pilus Adaptor Subunit PapF
| Autor: | Gabriel Waksman, Alison E. Ashcroft, Gregory T. Costakes, R.J. Rose, Scott J. Hultgren, Han Remaut, Tina Daviter, Emanuele Paci, Denis Verger, Sheena E. Radford |
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| Přispěvatelé: | Department of Bio-engineering Sciences, Structural Biology Brussels, Verger D., Rose R.J., Paci E., Costakes G., Daviter T., Hultgren S., Remaut H., Ashcroft A.E., Radford S.E., Waksman G. |
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular MICROBIO Protein Conformation PROTEINS Protein subunit Molecular Sequence Data Molecular Chaperones/chemistry Sequence alignment Biology Periplasmic Proteins/chemistry Pilus Fimbriae Proteins/chemistry 03 medical and health sciences 0302 clinical medicine Protein structure Bacterial Proteins Bacterial Proteins/chemistry Structural Biology Computer Simulation Amino Acid Sequence Proton-Translocating ATPases/chemistry Molecular Biology Peptide sequence 030304 developmental biology 0303 health sciences Escherichia coli Proteins Molecular biology N-terminus Proton-Translocating ATPases kinetics Fimbriae Bacterial Escherichia coli Proteins/chemistry Biophysics Fimbriae Proteins Periplasmic Proteins Bacterial outer membrane Sequence Alignment Fimbriae Bacterial/chemistry 030217 neurology & neurosurgery Biogenesis Molecular Chaperones |
| Zdroj: | Structure. 16:1724-1731 |
| ISSN: | 0969-2126 |
| Popis: | P pili are important adhesive fibers involved in kidney infection by uropathogenic Escherichia coli. Pilus subunits are characterized by a large groove resulting from lack of a β strand. Polymerization of pilus subunits occurs via the donor-strand exchange (DSE) mechanism initiated when the N terminus of an incoming subunit interacts with the P5 region/pocket of the previously assembled subunit groove. Here, we solve the structure of the PapD:PapF complex in order to understand why PapF undergoes slow DSE. The structure reveals that the PapF P5 pocket is partially obstructed. MD simulations show this region of PapF is flexible compared with its equivalent in PapH, a subunit that also has an obstructed P5 pocket and is unable to undergo DSE. Using electrospray-ionization mass spectrometry, we show that mutations in the P5 region result in increased DSE rates. Thus, partial obstruction of the P5 pocket serves as a modulating mechanism of DSE. © 2008 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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