Structure of the DUF2233 Domain in Bacteria and the Stuttering-associated UCE Glycoprotein
|
Scientists from the Joint Center for Structural Genomics (JCSG) in the
Structural Genomics Division at SSRL in collaboration with the laboratory of
Dr. Stuart Kornfeld at the Washington University School of Medicine in St.
Louis have carried out the structural and biochemical investigation of the
enzyme involved in stuttering, the “Uncovering enzyme” (UCE).
UCE is involved in cellular recycling. It carries out its work in the Golgi
apparatus. Mutations in UCE are linked with metabolic disease in mice and
persistent stuttering in people. Using crystallographic data from SSRL’s
Beam Line 9-2, the researchers uncovered the 3-D structure of the
enzyme’s active site, which belongs to a novel protein family.
Specifically, the researchers were working on the structure of a novel
protein from one of the microbes in the human gut. The protein belonged to a
new family (DUF2233), with many members in bacteria and some in viruses.
However the family only had one representative in humans – UCE.
UCE plays a key role in the functioning of lysosomes, cellular sacs full of
digestive enzymes that break down bacteria, viruses and worn-out cell parts for
recycling. When this recycling process goes awry, it can cause rare metabolic
diseases such as Tay-Sachs and Gaucher, which often cause death in affected
children by their early teens. Three years ago, researchers discovered that
three mutations in UCE itself were linked to persistent stuttering that is
passed down in families. It is thought, but not yet proven, that these
mutations may impair the functioning of critical neurons involved in
speech.
Primary Citation
D. Das, W.-S. Lee, J. C. Grant, H.-J. Chiu, C. L. Farr, J. Vance, H. E. Klock, M. W. Knuth, M. D. Miller, M.-A. Elsliger, A. M. Deacon, A. Godzik, S. A. Lesley, S. Kornfeld and I. A. Wilson, "Structure and Function of the DUF2233 Domain in Bacteria and in the Human Mannose 6-Phosphate Uncovering Enzyme", J. Biol. Chem. 288, 16789 (2013) doi: 10.1074/jbc.M112.434977
Related Links
- Science Highlight – HTML / PDF
- SSRL Science Highlights Archive
- SSRL Beam Lines
- SLAC News Feature
Contact
Debanu Das, JCSG, SSRL Structural Genomics
