Stanford University School of Medicine scientists working in part at SSRL's Beam Line 11-1 have uncovered new molecular insights to the mechanism behind immune disorders such as asthma. Using protein x-ray crystallography at 3.0 Angstrom resolution, researchers Sherry LaPorte and Chris Garcia solved three structures of two signaling proteins known as "cytokines" in complex with their shared receptors, where these molecules help regulate immune system activity. The study was published as the cover story in the January 25 edition of the journal Cell.

Cytokines are a family of proteins and peptides responsible for transmitting information from cell to cell by binding with special receptors on cell surfaces. In the current study, Garcia and colleagues worked out three structures involving two separate cytokines-interleukin-4 (IL-4) and interleukin-13 (IL-13), which are associated with allergic asthma. Although both have very different signaling effects, IL-4 and IL-13 are known to bind with some of the same receptors.

The study revealed that, despite sharing common receptors, very different chemistries underlie the binding activities of IL-4 and IL-13, a feature that may play a direct role in immune system disorders such as asthma. The discovery could lead to future drug therapies that address these differences and help down-regulate the immune response that results in the life-threatening risks associated with an asthma attack.

Sherry L. LaPorte, Z. Sean Juo, Jana Vaclavikova, Leremy A. Colf, Xiulan Qi, Nicola M. Heller, Achsah D. Keegan and K. Christopher Garcia (2008). "Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System" Cell 132(2): 259-272.

To learn more about this research see the full scientific highlight at:
http://www- ssrl.slac.stanford.edu/research/highlights_archive/IL-4.html