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SLAC National Accelerator Laboratory

Structure of the DUF2233 Domain in Bacteria and the Stuttering-associated UCE Glycoprotein

July 2013 SSRL Science Summary (adapted from SLAC News Feature by Glennda Chui)


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


Debanu Das, JCSG, SSRL Structural Genomics

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