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/

Dipeptidyl peptidase IV (DPP IV/CD26) belongs to a non-classical subfa mily of serine-proteases. Sequence comparisons have identified Asp(599 ), Ser(624), Asp(657), Asp(702), and His(734) as highly conserved resi dues of mouse DPP IV. We previously reported the identification of Ser (624), Asp(702) and His(734) as the catalytic triad of mouse DPP IV (D avid, F., Bernard, A. M., Pierres, M., and Marguet, D. (1993) J. Biol. Chem. 268, 17247-17252). Using site-directed mutagenesis, we have sho wn here that substitution of Asp(599) for Ala (D599A) specifically dec reases the cell-surface expression of DPP IV in stably transfected mou se fibroblasts. The D599A mutant remained as a high mannose immature g lycoprotein and was rapidly degraded. This retention/degradation proce ss correlates with the generation of a beta strand in the C-terminal r egion of DPP IV as shown by three dimensional computer modeling. Our r esults suggest that conserved residue Asp(599) is important for the pr oper folding, glycosylation and transport of mouse DPP IV. (C) 1996 Ac ademic Press, Inc.