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Proteins. 2019 Oct 6. doi: 10.1002/prot.25821. [Epub ahead of print]

Lysosomal acid lipase does not have a propeptide and should not be considered being a proprotein.

Author information

1
Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Oslo University Hospital, Norway.
2
Department of Microbiology, Oslo University Hospital, Norway.
3
ELIXIR Norway, Department of Informatics, University of Oslo, Oslo, Norway.

Abstract

Lysosomal acid lipase (LAL) plays an important role in lipid metabolism by performing hydrolysis of triglycerides and cholesteryl esters in the lysosome. Based upon characteristics of LAL purified from human liver, it has been proposed that LAL is a proprotein with a 55 residue propeptide that may be essential for proper folding, intracellular transport or enzymatic function. However, the biological significance of such a propeptide has not been fully elucidated. In this study we have performed a series of studies in cultured HepG2 and HeLa cells to determine the role of the putative propeptide. However, by Western blot analysis and subcellular fractionation we have not been able to identify a cleaved LAL lacking the N-terminal 55 residues. Moreover, mutating residues surrounding the putative cleavage site at Lys76 ↓ in order to disrupt a proteinase recognition sequence, did not affect LAL activity. Furthermore, forcing cleavage at Lys76 ↓ by introducing the optimal furin cleavage site RRRR↓EL between residues 76 and 77, did not affect LAL activity. These data, in addition to bioinformatics analyses, indicate that LAL is not a proprotein. Thus, it is possible that the previously reported cleavage at Lys76 ↓ could have resulted from exposure to proteolytic enzymes during the multi-step purification procedure. This article is protected by copyright. All rights reserved.

KEYWORDS:

cholesterol ester storage disease; lysosomal acid lipase; molecular biology; mutation; proprotein

PMID:
31587363
DOI:
10.1002/prot.25821

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