Scientific Highlights
Contents |
[edit] Crystal structure of sodium galactose transpoter
Using data collected at beamline 5.0.2, researchers at the David Geffen School of Medicine at UCLA have solved the structure of a class of proteins known as sodium glucose co-transporters (SGLTs), which pump glucose into cells. These transport proteins are used in the treatment of chronic diarrhea, saving the lives of millions of children each year, Oral Rehydration Therapy.
A tantalizing observation made during the determination of the glucose transporter structure was the possibility for structural similarities with a previously crystallized neurotransmitter transporter molecule. Exploiting these similarities, along with computer modeling of structural dynamics, the researchers obtained the first atomic level evidence for the mechanism underlying transport of glucose and neurotransmitters (such as serotonin) into cells. These results provide a fundamental understanding of how membrane proteins function in a dynamic manner. Pharmaceutical companies already have extensive clinical trials underway to evaluate the use of inhibitors targeting SGLT1 and SGLT2 proteins to control blood glucose levels in diabetic patients by blocking intestinal glucose absorption and increasing glucose excretion into the urine and the findings of the present study will dramatically enhance the ability to rationally design these drugs.
Salem Faham,Akira Watanabe, Gabriel Mercado Besserer, Duilio Cascio, Alexandre Specht, Bruce A. Hirayama, Ernest M. Wright, Jeff Abramson. (www.sciencexpress.org, 3 July 2008 Page 1)
[edit] Mechanism of Plant Growth Regulation Hormone Auxin Revealed
The plant hormone Auxin regulates plant growth. It is known to regulate gene expression by binding to its receptor TIR1 and promoting ubiquitin-dependent degradation of Aux/IAA repressor proteins. A recent crystal structure of Auxin and its receptor, determined using data obtained at both the sector 5 and 8 beamlines of the BCSB, reveals a detailed mechanism of how the regulation occurs at a molecular level. See the original publication or the ALS science highlights for more details
Tan et al, (2007). Nature, 446, 640-645.
[edit] Structure of a Nuclear Pore Complex
 | The nuclear pore complex (NPC) regulates the exchange of macromolecmules between the nucleus and the cytoplasm. Consisting of up to thirty proteins, it is one of the largest supramolecular assemblies in eukaryotic cells. Hoelz and coworkers crystallized and solved a hetero-octamer segment of the complex. Their model proposes that this segment forms a curved vertical rod that connects four horizontally stacked rings, forming a cylindrical pore. |
K.-C. Hsia, P. Stavropoulos, G. Blobel, and A. Hoelz, Cell 131, 1313-1326 (2007)
[edit] Acid-sensing Ion Channels
Acid-sensing ion channels (ASICs) are eukaryotic proton-activated receptors important in the sensory information, such as perception of pain, learning and memory. The Gouaux group’s 1.9 A structure from beamlines 8.2.1 and 8.2.2 of an ASIC suggests a way in which proton binding leads to long-range conformational changes which allow gating.
J. Jasti et al, Nature 449, 316. (2007)
[edit] Structure and Receptor Specificity of an Avian Flu Antigen
 | Since late 2003, H5N1 has reached epizootic levels in domestic fowl in a number of Asian countries, including China, Vietnam, Thailand, Korea, Indonesia, Japan, and Cambodia, and has now spread to wild bird populations. More recently, the H5N1 virus has spread to bird populations across much of Europe and into Africa. Recently, researchers at the Scripps Institute determined the structure of the hemagglutinin (HA) from a highly pathogenic Vietnamese H5N1 influenza virus using beamline 8.2.2. HA, the principal antigen on the viral surface, is the primary target for neutralizing antibodies and is responsible for viral binding to host receptors, enabling the virus to enter the host cell. As such, the HA is an important target for both drug and vaccine development. Read more at the ALS scientific highlight is here. |
J. Stevens, O. Blixt, T.M. Tumpey, J.K. Taubenberger, J.C. Paulson, and I.A. Wilson, "Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus," Science 312, 404 (2006).
[edit] Bacterial DNA Polymerases: Racing Through the Cell
| This first structure of a subunit of a bacterial polymerase shows that it is strikingly different from eukaryotic polymerases, suggesting that DNA replication in bacteria may have evolved independently. Several unique features of the structure also suggest a way in which the polymerase works with the associated sliding clamp structure to loosely "hold" the DNA in a channel and facilitate rapid replication. |  |
M.H. Lamers et al, Cell 126, 881. (2006) [8.2.1, 8.2.2, 8.3.1, 12.3.1]