Pancreatic lipase-related protein type I: a specialized lipase or an inactive enzyme.
The existence of pancreatic lipase-related protein 1 (PLRP1) in vertebrates has been postulated based on the screening of pancreatic cDNA libraries from different species. In this paper, we report the presence of variable amounts of PLRP1 relative to colipase-dependent lipase (PL) in adults from several species. Only a very low lipase activity could be detected for native or recombinant PLRP1 using a large variety of substrates and conditions. Interestingly, this activity is dependent on the presence of bile salts and colipase and PLRP1 is shown to possess the same affinity as PL for colipase. Modelling investigations revealed some interesting differences between PLRP1 and PL, notably concerning substitutions in the C-terminal domain which might affect the bending motion of this domain relative to the N-terminal domain in PLRP1. The potential impact of these differences on the lack of lipase activity of PLRP1 was investigated using chimeric proteins designed by C-terminal domain exchange between dog PLRP1 and horse PL. Analysis of the catalytic properties of the chimera clearly indicated that the C-terminal domain exchange neither inactivates the horse enzyme nor results in an active dog PLRP1. From these findings, it can be concluded that the PLRP1 C-terminal domain is fully functional with respect to colipase binding. The lack of lipase activity or the still undetermined function of PLRP1 is likely to result mainly from particular features of the N-terminal domain.
Crenon
I
I
Unité de Bioénergétique et Ingénierie des Protéines, UPR 9036 CNRS, Marseille, France.
Foglizzo
E
E
Kerfelec
B
B
Vérine
A
A
Pignol
D
D
Hermoso
J
J
Bonicel
J
J
Chapus
C
C
D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002415:Cats; D003089:Colipases / Q000378:metabolism; D004285:Dogs; D006736:Horses; D008049:Lipase / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D011993:Recombinant Fusion Proteins; D017385:Sequence Homology; D013045:Species Specificity
D003089:Colipases; D011993:Recombinant Fusion Proteins; D008049:Lipase; C075987:pancreatic lipase-related protein 1