Protein-specific glycosylation: signal patches and cis-controlling peptidic elements.
The term 'protein-specific glycosylation' refers to important functional implications of a subset of glycosylation types that are under direct control of recognition determinants on the protein. Examples of the latter are found in the formation of the mannose-6-phosphate receptor ligand on lysosomal hydrolases, and in polysialylation of NCAM, which are regulated via conformational signal patches on the protein. Distinct from these examples, the beta4-GalNAc modification of N-linked glycans on a selected panel of proteins, such as carbonic anhydrase or glycodelin, was demonstrated recently to require specific protein (sequence) determinants proximal to the glycosylation site that function as cis-regulatory elements. Another example of such a cis-regulatory element was described for the control of mammalian O-mannosylation. In this case, the structural features of substrate sites within the mucin domain of alpha-dystroglycan are necessary, but not sufficient for determining the transfer of mannose to Ser/Thr. Evidence has been provided that an upstream-located peptide is also essential. Such cis-controlling elements provide a higher level of protein specificity, because a putative glycosylation site cannot result from a single point mutation. Here, we highlight recent work on protein-specific glycosylation with particular emphasis on the above-cited examples and we will try to link protein-specific glycosylation to function.
Hanisch
Franz-Georg
FG
Institute of Biochemistry II, Medical Faculty, University of Cologne, D-50931 Köln, Germany. franz.hanisch@uni-koeln.de
Breloy
Isabelle
I
D000595:Amino Acid Sequence; D000818:Animals; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D010455:Peptides; D011506:Proteins