The existence of pancreatic lipase-related protein 1 (PLRP1) in verteb
rates has been postulated based on the screening of pancreatic cDNA li
braries 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 coul
d 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 posse
ss the same affinity as PL for colipase. Modelling investigations reve
aled some interesting differences between PLRP1 and FL, notably concer
ning substitutions in the C-terminal domain which might affect the ben
ding motion of this domain relative to the N-terminal domain in PLRP1,
The potential impact of these differences on the lack of lipase activ
ity of PLRP1 was investigated using chimeric proteins designed by C-te
rminal domain exchange between dog PLRP1 and horse FL. Analysis of the
catalytic properties of the chimera clearly indicated that the C-term
inal 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 colipa
se binding. The lack of lipase activity or the still undetermined func
tion of PLRP1 is likely to result mainly from particular features of t
he N-terminal domain.