NSLS Activity Report 2006 - Brookhaven National Laboratory

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BEAMLINES X6A, X29 PUBLICATION P.D. Pawelek, N. Croteau, C. Ng-Thow-Hing, C.M. Khursigara, N. Moiseeva, M. Allaire, and J.W. Coulton, " Structure of TonB in Complex with FhuA, E. coli Outer Membrane Receptor," Science, 312, 1399-1402 (2006). FUNDING Canadian Institutes of Health Research FOR MORE INFORMATION James W. Coulton Department of Microbiology and Immunology McGill University james.coulton@mcgill.ca Bacteria, like most living organisms, need iron to survive. Because of the low bioavailability of iron, bacteria synthesize high-affinity, iron-chelating low molecular weight compounds called siderophores that form metal:siderophore conjugates. The size of a metal:siderophore conjugate like ferrichrome prohibits entry into the bacteria via simple diffusion through porin-like channels. Alternatively, bacteria have developed uptake systems for these conjugates. We study the Ferric Hydroxymate Uptake system (Fhu) that works as follows (Figure 1): The outer membrane receptor FhuA, a 22-strand β-barrel protein with a cork domain, binds iron-bound ferrichrome. TonB that has been energized by the ExbB/D cytoplasmic membrane complex comes into contact with FhuA and allows ferrichrome to pass into the periplasmic space. Once in that space, ferrichrome binds to the protein FhuD that brings it to the FhuB/C Authors (from left) Natalia Moiseeva, Marc Allaire, Nathalie Croteau, and Peter Pawelek STRUCTURE OF TonB IN COMPLEX WITH FhuA, E. COLI OUTER MEMBRANE RECEPTOR P.D. Pawelek 1 , N. Croteau 1 , C. Ng-Thow-Hing 1 , C.M. Khursigara 1 , N. Moiseeva 2 , M. Allaire 2 , and J.W. Coulton 1 1 Department of Microbiology and Immunology, McGill University, Canada; 2 National Synchrotron Light Source, Brookhaven National Laboratory Iron, an essential element for most living organisms, is highly insoluble at physiological pH, making it difficult for bacteria to acquire. In order to obtain sufficient amounts of iron, bacteria have developed high affinity uptake systems. For the first time, interactions between two proteins of the ferric hydroxymate uptake (Fhu) system are seen at atomic resolution. Crystals of a complex of outer membrane receptor FhuA and its energizing partner, TonB, give us insights into the mechanism by which E.coli acquires iron. Learning about this mechanism could help in the development of targeted antibiotics. 2-62 complex, an ABC transporter that finally transports it into the cytoplasm. We first showed that upon binding of the ferrichrome-iron conjugate, a conformational change is transmitted to the periplasmic side of FhuA, resulting in the unwinding of a switch helix, thus signaling the ligand-loaded status of the receptor (Figure 2A,B). The next step involves the binding of TonB to the FhuA receptor; however the molecular mechanism whereby this occurs was unknown. By obtaining diffraction-quality crystals of a 1:1 FhuA:TonB complex and the use of synchrotron radiation, we have been able to shed light on how ferrichrome enters the periplasmic space. The resulting crystal structure of this complex reveals that residues from the FhuA Ton box form a parallel β-interaction with the β3-strand of the central β-sheet of the C-terminal domain of TonB (Figure 2C). This interaction positions the highly conserved TonB residue, Arg166, to contact FhuA residue Glu56, which is also located in a conserved motif. From this we are able to predict the functional importance of this FhuA-TonB ionic interaction. What does the crystal structure of the FhuA-TonB complex tell us about interactions of TonB with a cognate OM receptor and the transport of metalchelated siderophore? From our structural data combined with findings from previous studies, we propose that the interprotein β-sheet formed between the receptor Ton box, and the C-terminal domain of TonB is required to position the TonB helix close to the receptor cork domain. In the FhuA-TonB structure, this results in TonB Arg166
forming an electrostatic interaction with FhuA cork residue Glu56. It was recently proposed that hydration of the cork domain may render it prone to disruption by TonB through transmission of a relatively small force perpendicularly applied to it. Figure 1. The Ferric Hydroxymate Uptake system (Fhu) 2-63 Given its position proximal to the FhuA cork domain, TonB Arg166 is positioned to mediate such a mechanical shearing or pulling force to the cork domain. This may result in cork disruption, allowing siderophore translocation into the periplasm. A B Figure 2. Changes occurring at the periplasmic side of FhuA. (A) Prior to iron-ferrichrome conjugate binding on the FhuA receptor. (B) Unwinding of the switch helix upon iron-ferrichrome conjugate binding. (C) Binding of the C- Terminal domain of TonB to the FhuA conserved Ton box. C LIFE SCIENCE
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NATIONAL SYNCHROTRON LIGHT SOURCE A
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NATIONAL SYNCHROTRON LIGHT SOURCE 2
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NSLS Summer Sunday Draws 650 Visito
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CHAIRMAN'S INTRODUCTION Chi-Chang K
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USERS' EXECUTIVE COMMITTEE REPORT C
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SCIENCE AT THE NSLS Kendra Snyder N
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Spin-Lattice Interaction in the Qua
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SOFT CONDENSED MATTER AND BIOPHYSIC
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grows. The magnesium also is attrac
Page 19 and 20: Chicago, Liangtao Li and Jerry Kapl
Page 21 and 22: STRUCTURE OF AN E. COLI MEMBRANE PR
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in Farmingville, New York. She inve
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egan with three days of lectures an
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Participants in the 2006 “Take ou
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While Dehmer was optimistic about t
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Next, a talk on the “Engineering
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Energy Secretary Samuel Bodman (fro
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with majors ranging from history to
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described the first measurements of
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Visitors gather around the liquid n
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high-level degree in the physics fi
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Spotlight Awards The Spotlight awar
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A) B) Figure 1. X-ray fl uorescence
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BNL WINS R&D 100 AWARD FOR X-RAY FO
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2005 Hans-Jürgen Engell Prize The
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2006 NSLS TOURS 1/4/2006 Karen Agos
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2006 NSLS SEMINARS 1/11/2006 Interi
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2006 NSLS SEMINARS 6/22/2006 Strate
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2006 NSLS WORKSHOPS 4/4/2006 X6A Wo
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NATIONAL SYNCHROTRON LIGHT SOURCE O
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NSLS ADVISORY COMMITTEES GENERAL US
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ACCELERATOR DIVISION REPORT James B
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On-Axis Field (gauss) VTF Test Arti
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The NSLS has an aggressive preventi
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tific workshops, including “Synch
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ently the last one available in the
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functions, particularly at the nano
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A new Proposal Oversight Panel (POP
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SAFETY REPORT Andrew Ackerman ESH&Q
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BUILDING ADMINISTRATION REPORT Bob
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ing were cleaned, repaired, and pai
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FACILITY FACTS & FIGURES The Nation
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Beamline Source Technique Energy Ra
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NSLS BOOSTER PARAMETERS NSLS LINAC
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X-RAY STORAGE RING PARAMETERS AS OF
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PUBLICATIONS
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NSLS USERS Beamline U1A S Buzby, M
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A Nambu, J Graciani, J Rodriguez, Q
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Beamline X1A2 M Feser, B Hornberger
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C Mandel, D Gebauer, H Zhang, L Ton
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Beamline X7A E Anokhina, Y Go, Y Le
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T Moldoveanu, Q Liu, J Tocilj, M Wa
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Beamline X10A A Cisneros, G Mazzant
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S Kamtekar, R Ho, M Cocco, W Li, S
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Z Zhang, P Fenter, S Kelly, J Catal
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E Selvi, Y Ma, R Aksoy, A Ertas, A
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Y Suh, M Carroll, R Levy, G Bisogni
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S Park, E DiMasi, Y Kim, W Han, P W
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G Da, J Lenkart, K Zhao, R Shiekhat
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J Kaste, B Bostick, A Friedland, A
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X Chen, K Tenneti, C Li, Y Bai, R Z
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G Meinke, P Bullock, A Bohm, Crysta
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D Koller, G Ediss, L Mihaly, G Carr
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NSLS Activity Report 2006 - Brookhaven National Laboratory

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