Glycobiology Advance Access originally published online on December 15, 2006
Glycobiology 2007 17(5):455-466; doi:10.1093/glycob/cwl079
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Crystal structure of mammalian 
1,6-fucosyltransferase, FUT8
2 Department of Disease Glycomics, Research Institute for Microbial Diseases, Osaka University, Taniguchi Research Group, 4th Floor, Center for Advanced Science & Innovation, Osaka University, 2-1, Yamadaoka Suita, Osaka 565-0871, Japan
3 Division of Molecular Cell Biology, Department of Biomolecular, Sciences, Saga University Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
4 Core Research for Evolution Science and Technology (CREST), Japanease Science and Technology Agency (JST), 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
5 Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo 7-3-1, Tokyo, Bunkyo-ku, 113-0033, Japan
6 Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan
7 Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
8 Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan
9 Department of Molecular Genetics, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan
1 To whom correspondence should be addressed; e-mail: tani52{at}wd5.so-net.ne.jp
Received on October 30, 2006; revised on November 30, 2006; accepted on December 1, 2006
Mammalian 
1,6-fucosyltransferase (FUT8) catalyses the transfer of a fucose residue from a donor substrate, guanosine 5'-diphosphate-ß-L-fucose to the reducing terminal N-acetylglucosamine (GlcNAc) of the core structure of an asparagine-linked oligosaccharide. 1,6-Fucosylation, also referred to as core fucosylation, plays an essential role in various pathophysiological events. Our group reported that FUT8 null mice showed severe growth retardation and emphysema-like lung-destruction as a result of the dysfunction of epidermal growth factor and transforming growth factor-ß receptors. To elucidate the molecular basis of FUT8 with respect to pathophysiology, the crystal structure of human FUT8 was determined at 2.6 Å resolution. The overall structure of FUT8 was found to consist of three domains: an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The catalytic region appears to be similar to GT-B glycosyltransferases rather than GT-A. The C-terminal part of the catalytic domain of FUT8 includes a Rossmann fold with three regions that are conserved in 1,6-, 1,2-, and protein O-fucosyltransferases. The SH3 domain of FUT8 is similar to other SH3 domain-containing proteins, although the significance of this domain remains to be elucidated. The present findings of FUT8 suggest that the conserved residues in the three conserved regions participate in the Rossmann fold and act as the donor binding site, or in catalysis, thus playing key roles in the fucose-transferring reaction.
Key words: fucosyltransferase / core fucosylation / N-glycan / crystal structure / glycosyltransferase