Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene

Wen Wei, Karl Hackmann, Hangxue Xu, Gregory Germino, Feng Qian

Research output: Contribution to journalArticlepeer-review

Abstract

Polycystin-1 (PC1), the PKD1 gene product, plays a critical role in renal tubule diameter control and disruption of its function causes cyst formation in human autosomal dominant polycystic kidney disease. Recent evidence shows that PC1 undergoes cleavage at the juxtamembrane G protein-coupled receptor proteolytic site (GPS), a process likely to be essential for its biological activity. Here we further characterized the proteolytic cleavage of PC1 at the GPS domain. We determined the actual cleavage site to be between leucine and threonine of the tripeptide HLT3049 of human PC1. Cleavage occurs in the early intracellular secretory pathway and requires initial N-glycan attachment but not its subsequent trimming. We provide evidence that the cleavage occurs via a cis-autoproteolytic mechanism involving an ester intermediate as shown for Ntn hydrolases and EMR2.

Original languageEnglish (US)
Pages (from-to)21729-21737
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number30
DOIs
StatePublished - Jul 27 2007

ASJC Scopus subject areas

  • Biochemistry

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