title: Reduced cell surface expression of a mutated dipeptidyl peptidase IV (DPP IV/CD26) correlates with the generation of a beta strand in its C-terminal domain.
abstract: Dipeptidyl peptidase IV (DPP IV/CD26) belongs to a non-classical subfamily of serine-proteases. Sequence comparisons have identified Asp599, Ser624, Asp657, Asp702, and His734 as highly conserved residues of mouse DPP IV. We previously reported the identification of Ser624, Asp702 and His734 as the catalytic triad of mouse DPP IV (David, F., Bernard, A. M., Pierres, M., and Marguet, D. (1993) J Biol. Chem. 268, 17247-17252). Using site-directed mutagenesis, we have shown here that substitution of Asp599 for Ala (D599A) specifically decreases the cell-surface expression of DPP IV in stably transfected mouse fibroblasts. The D599A mutant remained as a high mannose immature glycoprotein and was rapidly degraded. This retention/degradation process correlates with the generation of a beta strand in the C-terminal region of DPP IV as shown by three dimensional computer modeling. Our results suggest that conserved residue Asp599 is important for the proper folding, glycosylation and transport of mouse DPP IV.
authors.affiliation: INSERM U 410, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: David
authors.forename: L
authors.initials: L
authors.lastname: Baricault
authors.forename: C
authors.initials: C
authors.lastname: Sapin
authors.forename: X
authors.initials: X
authors.lastname: Gallet
authors.forename: D
authors.initials: D
authors.lastname: Marguet
authors.forename: A
authors.initials: A
authors.lastname: Thomas-Soumarmon
authors.forename: G
authors.initials: G
authors.lastname: Trugnan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism* / Q000648:ultrastructure; D006031:Glycosylation; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: D018832:Molecular Chaperones; D011994:Recombinant Proteins; D001224:Aspartic Acid; D018819:Dipeptidyl Peptidase 4