As a result of stresses such as heat shock, a protein can lose its natural fold, enabling it to aggregate with other unfolded proteins. If this process isn't combated then cells die. Chaperonins are proteins found in everything from microbes to humans, that come to the rescue to help mis-folded proteins regain their correct fold so they can work properly within the cell. Paul Adams and his collaborators examined crystallographic data from the chaperonin GroEL, found in E. coli, and were able to extract information about the large scale motions of the molecule during different stages of its reaction cycle. These results derived from experimental data are similar to those that previously could only be predicted by computational modeling studies. The technique may provide a method for examining other large complexes to further our understanding of molecular machines. The full results of Adams’ study are published in the September 3rd 2004 issue of the Journal of Molecular Biology, and in Berkeley Lab's Science Beat.

Additional highlights in Structural Biology

Crystal structure and mechanism of calcium-gated potassium channels
Rod MacKinnon shared the 2002 Nobel Prize in Chemistry for studies involving cell membrane channels. Using BCSB beamline 8.2.2, MacKinnon revealed the 3-D structure of ion channels, which regulate the passage of inorganic ions through membranes. Ion channels control heart rate, regulate hormones, and generate electrical signals in the nervous system. MacKinnon’s work is opening new research in biochemistry and biology.

Solving the structure of the 70S ribosome
Henry Noller of UCSC, collaborating with LBNL researchers in 2001, solved the structure of the complete 70S ribosome by X-ray crystallography to a resolution of 5.5 Å. This work revealed how the messenger RNA and transfer RNAs bind to the ribosome during protein synthesis, and how the two ribosomal subunits interact with one another. It also led to the conclusion that ribosomal RNA, rather than the ribosomal proteins, appear to provide the main functional interactions with mRNA and tRNA. At a molecular weight of 2.5 million, the ribosome is still the largest asymmetric molecular structure ever solved by crystallography.

AcrB Multidrug Efflux Pump
In healthy people, multidrug efflux pumps play important roles, such as preventing the entry of toxic molecules across the blood-brain barrier. But when overexpressed, they can make cancer cells resistant to a wide range of chemotherapy drugs by simply expelling them. A team including Daniel E. Koshland, Jr., Hiroshi Nikaido,
Edward Wa Yu (UC Berkeley) and Helen Zgurskaya (University of Oklahoma) completed its structural studies at the BCSB providing insights into how to build more effective drug therapies that are resistant to the efflux pump.

Improving the Efficacy of the Leukemia Drug Gleevec
John Kuriyan identified the structural changes caused by gene mutations that render the drug Gleevec ineffective in some patients who have chronic myeloid leukemia (CML). The findings will help researchers improve the effectiveness of second-generation drugs that will reduce drug resistance. The development may also allow for sophisticated genetic screening to identify best therapies for individual CML patients.