1 . FIRST PROTEIN STRUCTURE OF A KEY MOLECULAR ENGINE
By Art Robinson
(Contact: SHKim@lbl.gov)

ABC transporters (also known as traffic ATPases) form a large family of proteins responsible for movement of biochemical compounds through cell membranes. Researchers from Berkeley Lab and the University of California, Berkeley, have used the Macromolecular Crystallography Facility at the ALS to obtain the crystal structure of the HisP subunit of histidine permease, an ABC transporter from Salmonella typhimurium. (The results can be viewed on the Web at http://www-als.lbl.gov/als/science/sci_archive/hisp.html.) The structure, obtained with a resolution of 1.5 Å, provides a basis for understanding properties of both normal and defective ABC transporters.

ABC transporters variously act as pumps that propel substances through membranes, as channels that allow the substances' passage, and as regulators that control other membrane proteins. Their general structural features, known from biochemical studies, include membrane-spanning domains between which the transported substances pass and nucleotide-binding domains, which are the molecular engines that drive the pumps or open and close the channels by using the energy released in the binding and hydrolysis of adenosine triphosphate (ATP). ABC transporters are increasingly recognized as the causes of human genetic diseases, such as cystic fibrosis--a lethal disease that occurs in about 1 in 3,300 live births in the United States and Canada.

In S. typhimurium, histidine permease contains two identical nucleotide-binding domains, known as HisP, that together form a dimer. Using multiple-wavelength anomalous diffraction (MAD) methods to obtain phase information about a diffracted x-ray beam, the Berkeley group has solved the structure of HisP with a resolution of 1.5 Å. A four-wavelength MAD data set was obtained in just two hours at the ALS. The structure of the HisP monomer exhibits an unusual L shape with two thick arms, one of which holds the ATP binding site and the other of which is proposed to be in contact with a membrane-spanning domain. It is possible that binding and hydrolysis of ATP in one arm results in conformational changes in the other arm that are passed on to the membrane-spanning domain, but the mechanism is not yet known in any detail. The purpose of the dimer structure, which results in two molecular engines, is also not yet known.

Because of the substantial similarity of the nucleotide-binding domains in both prokaryotic cells (such as Salmonella typhimurium) and eukaryotic cells (such as those in humans), structural details found in one type of organism are expected to apply to others. For example, the ability of the researchers to correlate the properties of mutant forms of the cystic fibrosis transmembrane conductance regulator (CFTR), an ABC transporter involved in cystic fibrosis, with the crystal structure of HisP indicates that HisP is a good model for the nucleotide-binding domains of ABC transporters in general.

The Berkeley researchers used their HisP findings to propose a structural basis for the consequences of the known CFTR mutations. The most common mutation, found in 90% of all cystic fibrosis patients, leads to incorrect protein folding and transit. Other mutations may inhibit ATP binding or hydrolysis, thereby turning off the engine, or disrupt the interaction with the membrane-spanning domains, thereby putting the engine in neutral. This kind of information may eventually lead to a treatment for cystic fibrosis.

Research conducted by L.-W. Hung (Berkeley Lab); I. X. Wang, K. Nikaido, P.-Q. Liu, and G. F.-L. Ames (University of California, Berkeley); and S.-H. Kim (University of California, Berkeley, and Berkeley Lab), using Beamline 5.0.2.

Publication about this experiment: L.-W. Hung et al., Nature 396, 703 (1998).

Funding: U. S. Department of Energy, Office of Biological and Environmental Research; National Institutes of Health.

2. THIRD-HARMONIC CAVITY UPDATE
(Contact: JMByrd@lbl.gov)

One of the key installations made during the June shutdown was the placement of a series of rf cavities in storage-ring Sector 2. The five cavities, tuned to the third harmonic of the main rf frequency in the storage ring, are expected to triple electron bunch lengths. This greater "elbow room" for electrons should, in turn, decrease large-angle intrabunch scattering (Touschek scattering) and thereby increase beam lifetime. (Beam lifetimes in the ALS storage ring are dominated by the Touschek effect because of the low transverse emittances. Gas scattering lifetimes are an order of magnitude longer.) Lifetime increases of a factor of two to three should result. Like anything worth having, however, reaching the design goals will take time and effort. Initial accelerator physics studies have been optimistic, though more studies will be required over the next three to six months before users will see the longer lifetimes. In tests conducted after the shutdown, bunch lengths of 2.5 times the usual were observed. Another positive sign is that initial accelerator work has already restored storage-ring lifetime and stability to what they were before the introduction of the new devices into the ring.

3. NEW FEATURE COMING: UEC CORNER
(Contact: kevan@oregon.uoregon.edu)

Beginning with our next issue, the ALS Users' Executive Committee (UEC) will give ALSNews readers biweekly updates on UEC business and activities. This new feature will be written by UEC Chair Stephen D. Kevan and Vice Chair Nora Berrah. The UEC hopes to broaden its channels of communication with ALS users in order to better serve their needs. For those who can't wait until the next issue, more information about the UEC is available on the Web at http://www-als.lbl.gov/als/uec/index.html. As always, users are welcome to contact the UEC Chair directly by email at kevan@oregon.uoregon.edu or by phone at (541) 346-4742.

4. FRIDAY SCHEDULING MEETINGS DISCONTINUED
(Contact: GFKrebs@lbl.gov)

The scheduling meetings for users, held on Fridays at 3:30, have been discontinued. In the past year or so, this meeting has been generally unattended by users, except for those requesting the special operations "scrubbing" shift. User requests for special operations use of the "scrubbing" shift should now be sent directly to Bob Miller by Friday at 1:00 p.m. The long-term schedule is posted on the web (at http://www-als.lbl.gov/als/schedules/current_ltsch.html) as well as in various locations on the experiment floor, including the users' bulletin board. In the future, the meeting can be reinstated should the need arise for users.

5. MICRO-XAS AND MICROFLUORESCENCE WORKSHOP JULY 30
(Contact: thompson@lbl.gov)

The ALS will host a Micro-XAS and Microfluorescence Workshop on July 30. Sessions will be held in the conference room on the ALS mezzanine (Building 6, Room 2202). The meeting will address all aspects of micro-x-ray absorption spectroscopy and microfluorescence research, with an emphasis on synchrotron radiation studies. Presentations will include talks by scientists from the ALS, the European Synchrotron Radiation Facility, the Advanced Photon Source, and the Center for Advanced Microstructures and Devices. Plans for upgrading ALS Beamlines 10.3.1 and 10.3.2 will also be presented. For further details, contact Al Thompson at thompson@lbl.gov or phone (510) 486-5590.

6. PAIR OF POSTDOCTORAL POSITIONS AVAILABLE
(Contact: Tobin1@llnl.gov)

The Chemistry and Materials Science Directorate, Materials Science and Technology Division of the Lawrence Livermore National Laboratory (LLNL), has two postdoctoral research positions beginning in the summer or fall of 1999. Duties include investigating the electronic, geometric, and magnetic structures in nanocrystals, surfaces, ultrathin films, multilayers, foils, and single crystals using x-ray absorption, photoelectron spectroscopy, and photoelectron diffraction, particularly the electron-spin-polarized and x-ray-dichroic variants. The two openings will be in (1) 3d and 4f magnetic materials and (2) actinide research. Work will be performed primarily at the Advanced Light Source. Candidates must have a recent Ph.D. in chemistry, physics, materials science, or a related field. Previous experience with synchrotron radiation, and American citizenship are preferred. Interested parties should send curriculum vitae, educational transcripts for the last five years, and three letters of reference to

Dr. James G. Tobin
c/o Ms. Kathy Copp
Lawrence Livermore National Laboratory
7000 East Ave., POB 808, L-357
Livermore, CA 94550
Tel.: 925-422-7247
Fax: 925-423-7040
Email: Tobin1@llnl.gov

Further information is available in the June issue of Physics Today and on the Web at http://www-cms.llnl.gov/recruiting/join_team.html or at http://www.llnl.gov/jobs.

7. WHO'S IN TOWN: A SAMPLING OF ALS USERS

To highlight the richness of our user community and help introduce recent arrivals, we offer this listing of some of the experimenters who will be collecting data during the next two weeks at the ALS.

Beamline 1.4.3: Ted Raab (Univ. of Colorado, Boulder) will continue studies of rhizosphere plant root/soil interactions with the IR microscope. Felicia Hendrickson and Robert Glaeser (Berkeley Lab) will continue mapping the photocycle of bacteriorhodopsin microcrystals. Hoi-Ying Holman (Berkeley Lab) will monitor cell/toxin interactions by using FTIR spectromicroscopy.

Beamline 6.3.2: Ivan Dominguez-Lopez and Lan Dang [both of Univ. of Nevada, Las Vegas (UNLV)], Colin Cunliff (Univ. of Texas, summer intern through UNLV), and Gunnar Ohrwall (Berkeley Lab and UNLV) will conduct gas-phase ion spectroscopy experiments, making absorption and branching-ratio measurements on some simple molecules and on carbonyl sulfate. Also, Linda Sapochak, Gregory Schmett, Asanga Padmaperuma, Nancy Washton, and Flocerfida Endrino (UNLV) and Nimel Theodore (Drew Univ., summer intern) will be performing x-ray absorption by total photocurrent measurements of important emitter materials used in organic light-emitting devices (a series of metal quinolate chelates).

Beamline 7.3.1.1: Zi Qiang Qiu and his students (Univ. of California, Berkeley) will continue their work on exchange-coupled multilayers using PEEM2, and Adam Hitchcock (McMaster Univ., Ontario) will use PEEM2 to investigate polymers.

Beamline 8.0: Oliver Hemmers (UNLV), Pedro Focke (Univ. of Tennessee), Marcello Sant' Anna (Berkeley Lab), Jason Fong (Univ. of California, Berkeley), Ralf Wehlitz (Synchrotron Radiation Center, Madison), Melanie Blackburn (Univ. of West Virginia, DOE summer intern), and Tara Goddard (Univ. of California, Santa Barbara, DOE summer intern) will be performing gas-phase electron spectroscopy experiments, including multi-atom resonant photoemission, and first- and second-order corrections to the dipole approximation.

Beamline 9.3.1: Paul Neill and Jim Cotter (both of Univ. of Nevada, Reno) and Wayne Stolte (UNLV and Berkeley Lab) will be conducting gas-phase ion spectroscopy experiments (absorption and branching-ratio measurements) on carbonyl sulfate and some freon molecules.

8. OPERATIONS UPDATE
(Contact: RMMiller@lbl.gov)

Long-term and weekly operations schedules are available on the Web (http://www-als.lbl.gov/als/accelinfo.html). Requests for special operations use of the "scrubbing" shift should be sent to Bob Miller (RMMiller@lbl.gov, x4738) by 1:00 p.m. Friday. The Accelerator Status Hotline at (510) 486-6766 (ext. 6766 from Lab phones) features a recorded message giving up-to-date information on the operational status of the accelerator.