Protein Structure Suggests Role as Molecular Adapter
To split and copy DNA during replication, all cellular organisms use a multicomponent molecular machine known as the replisome. An essential step in replisome assembly is the loading of ring-shaped helicases (motor proteins) onto the separated strands of DNA. Dedicated ATP-fueled proteins regulate the loading; however, the mechanism by which these proteins recruit and deposit helicases has remained unclear. To better understand this process, researchers at the University of California, Berkeley, recently determined the structure of the ATPase region of DnaC, a bacterial helicase loader. The structure revealed that DnaC is a close cousin of DnaA, the protein thought to be responsible for unwinding DNA. Unexpectedly, the team further found that DnaC forms a right-handed helix similar to the state adopted by ATP-bound DnaA. These findings, together with biochemical studies, implicate DnaC as a molecular adapter that uses ATP-activated DnaA as a docking site for ensuring that DnaB (the ring-shaped helicase) is correctly deposited at the onset of replication. Read more…
Publication about this research: M.L. Mott, J.P. Erzberger, M.M. Coons, and J.M. Berger, “Structural synergy and molecular crosstalk between bacterial helicase loaders and replication initiators,” Cell 124, 623 (2009).
Another Landmark Development in Biological Microscopy at the ALS
The biotech, pharmaceutical, and biofuels industries all grew out of our ability to understand and then predict how cells respond to changes in their environment. For example, the quest to make biofuel production more efficient begins with understanding how the cells that carry out fermentation deal with increasingly toxic concentrations of alcohol or butanol, taking advantage of this knowledge to guide the development of organisms with increased tolerance toward these molecules. Microscopy is a key technology in such work, in particular, high-resolution three-dimensional methods such as soft x-ray tomography. The establishment of the National Center for X-Ray Tomography (NCXT) and the construction of XM-2 firmly put the ALS on the map as a premier facility for imaging cells. Recently, the ALS became home to a completely new bio-imaging method: cryogenic, high-numerical-aperture light microscopy.
Developed by Mark Le Gros and Carolyn Larabell of the NCXT, this new microscope satisfies a long-standing need in cellular imaging. Now, for the first time, it is possible to image a whole, hydrated cell at high spatial resolution using both light and soft x rays. Correlation of the two data sets allows visualization of detailed cellular structure (x rays) together with the location of molecules tagged with a fluorescent label (light). The combination of these two pieces of knowledge is the “Holy Grail” of cell biology and answers the fundamental questions of who, what, where, and when. In other words, which molecules are interacting, and where and when do these interactions occur in the cell. This is a very exciting development in the world of cellular imaging, with the ALS being the only facility in the world with this capability. This new multimodal imaging resource has already begun to be used to address a wide range of highly topical questions, ranging from the design of new drugs to fight malaria and fungal infections to understanding where biodiesel is stored in algae. The possible applications of this new technique are virtually limitless, and it opens up a new chapter in biological research at the ALS.
The new cryo-light microscope used in this work is described in detail in the paper, “High aperture cryogenic light microscopy,” by M.A. Le Gros, G. McDermott, M. Uchida, C.G. Knoechel, and C.A. Larabell, to be published in the July 2009 issue of the Journal of Microscopy.
Call for General User Proposals: Upcoming Deadlines
The User Services Office is accepting general user proposals from scientists who wish to conduct research at the ALS in the next cycle.
PROPOSAL SUBMISSION DEADLINE (physical sciences beamlines):
PROPOSAL SUBMISSION DEADLINE (structural biology/biological SAXS):
NEW PROPOSALS: To submit a new proposal, please complete the appropriate online form.
ACTIVE PROPOSALS: Proposals for physical sciences beamlines are considered active and may be renewed for up to three, six-month cycles after the initial submission. After a total of four cycles, a new proposal must be submitted. If you have an active proposal for which you would like to request beam time during the January 2010–June 2010 cycle, please submit a Proposal Renewal Form.
The following resources have been recently updated and are available for further information:
General information on the proposal process
The proposal form now includes a section on publications from previous ALS work. The publications will be pre-filled automatically from the ALS publication database by searching for the principal investigator’s name. Please make sure your publications are entered into our database.
UEC Corner: ALS Users’ Meeting Important Dates
Contacts: Ken Goldberg, Yayoi Takamura, David Osborn
The 16th annual ALS Users’ Meeting is just a few months away: October 15–17, 2009. As in 2007, this year’s meeting will be held jointly with The Molecular Foundry, with joint plenary and poster sessions, workshops, and a banquet. Information will be posted on the Users’ Meeting Web site as it becomes available.
WORKSHOPS: This year’s meeting will have a primary focus on research to further the United States’ and the world’s energy agenda. Workshops cover that theme and a broad spectrum of other issues, including detectors; x-ray diffraction; graphene; influenza; nanomagnetism; next-generation light sources; numerical modeling; quantum systems, clusters, and assembled materials; spectroscopy; tailored materials; and polymers.
AWARDS: Nominations for the Shirley (Science), Halbach (Instrumentation), and Renner (Service) Awards will accepted until Monday, August 31, 2009. This year’s nomination process will be a bit different than in previous years. Please check the Users’ Meeting Web site in July for details.
POSTERS: The deadline for poster abstract submissions is Monday, August 31, 2009. Students submitting posters have the opportunity to compete for three poster awards, with the winner being given an opportunity to speak at the Friday morning session.
LODGING: The Berkeley Lab Guest House is nearing completion, and we expect that it will be ready to accept guests by the time of the meeting. However, reservations are not being accepted just yet. Check the above link frequently if you’d like to be one of the first guests. A block of rooms has also been reserved at the Hotel Durant.
UEC ELECTIONS: Finally, the ALS Users’ Executive Committee will be electing three new members and one student representative this fall. Nominations will be accepted until October 15, 2009, and voting will begin on October 16, 2009, on the second day of the meeting. Nomination instructions will be provided on the ALS Users’ Meeting Web site in July.
Update on the Guest House at Berkeley Lab
Located within a short walk of the ALS and the cafeteria, the 57-room guest house will provide 70 beds in single- and double-occupancy rooms, and will include a main lobby, lounge/kitchenette area, laundry facilities, vending areas, and an outdoor patio. All rooms will have a refrigerator and free wireless Internet access.
Construction of the guest house is nearing completion, with electrical and air-conditioning commissioning starting this week. Furniture has been ordered and will be fitted in August, to be followed by further commissioning and staff training. An interim general manager is in place and work on the Web site is progressing. The opening date is currently being negotiated with the operating contractor and is likely to be the first week of October. The rates for staying at the guest house will be set within the next couple of weeks and will depend on the size and occupancy of the room with a slight premium for a bay view. The operator can now take reservations for groups of 10 rooms or more. Starting September 1, 2009, the operator will take reservations for individuals or groups booking fewer than 10 rooms. Reservations can be made by contacting Megan Troup (510-643-2454).
Job Opportunity: ALS Writer-Editor
The Advanced Light Source seeks a dynamic, creative writer to create and edit printed documents and electronic media to communicate the mission and achievements of the ALS. The writer will support the scientific and user programs of the ALS through the production of publications by working with scientists and technical staff to create visual displays, presentation materials, and grant proposals.
A primary role is to plan, edit, produce, and distribute a monthly email newsletter designed to keep ALS researchers and other interested parties informed about developments at the ALS. It will require the incumbent to apply broad knowledge of ALS research programs, scientific and engineering concepts, and Berkeley Lab’s publication processes to communicate technical and nontechnical information for publication or verbal presentation. Will use Web 2.0 and social networking technologies to expand readership and to develop new audiences.
Read more at the official job posting.
For the user runs from May 13 to June 15, the beam reliability [(time scheduled – time lost)/time scheduled)] was 96.0%. For this period, the mean time between failures (MTBF) was 38.9 hours, and the mean time to recovery (MTTR) was 96 minutes. There were no significant interruptions.
During this period we set a new record for continuous hours of light provided to users in top-off mode: 95 continuous hours of light were provided to users from June 4 to June 7.
More detailed information on reliability is available on the ALS reliability bulletin board, which is located in the hallway between the ALS and the control room in Building 80. Questions about beam reliability should be directed to David Richardson (x4376 ).
Long-term and weekly operations schedules are available here. Requests for special operations use of the “scrubbing” shift should be sent to Rick Bloemhard (ALS-CR@lbl.gov, x4738) by 1:00 p.m. Friday. View the ring status in real time here.