Biosynthesis and function of beta 1,6 branched mucin-type glycans.
The contribution of carbohydrate structure to biomolecular, cellular, and organismal function is well-established, but has not yet received the attention it deserves, perhaps due to the complexity of the structures involved and to a lack of simple experimental methods for relating structure and function. In particular, beta1,6 GlcNAc branching plays a key functional role in processes ranging from inflammation and immune system function to tumor cell metastasis. For instance, synthesis of the core 2 beta1,6 branched structure in the mucin glycan chain by C2GnT enables the expression of functional structures at the termini of polylactosamine chains, such as blood group antigens and sialyl Lewis x. Also, IGnT can create multiple branches on the polylactosamine chain, which may serve as a mechanism for amplifying the functional potency of cell surface glycoproteins and glycolipids. The family of enzymes which creates beta1,6 branched structure in mucin glycans is proving to be quite complex, since multiple isoforms appear to exist for these enzymes, and some of the enzymes are adept at forming more than one type of beta1,6 branched structure, as in the case of C2GnT-M. Furthermore, the enzymes do not appear to be restricted to acting on mucin-type acceptor structures, but are able to act on glycolipid structures as well. Much remains to be learned regarding the specific biological niche filled by each of these enzymes and how their activities complement one another, as well as the manner in which the activities of these enzymes are regulated in the cell.
Beum
P V
PV
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center Omaha, NE 68198-4525, USA.
Cheng
P W
PW
D015061:1,4-alpha-Glucan Branching Enzyme / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009077:Mucins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D018076:DNA, Complementary; D009077:Mucins; D011134:Polysaccharides; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases; D015061:1,4-alpha-Glucan Branching Enzyme