COOH-terminal requirements for the correct processing of a phosphatidylinositol-glycan anchored membrane protein.

Journal Article (Journal Article)

Placental alkaline phosphatase (PLAP) is anchored to the plasma membrane by a phosphatidylinositol-glycan (PI-G) moiety. During processing of nascent PLAP, a 29-residue COOH-terminal peptide is cleaved out and the PI-G moiety is attached to the newly created COOH terminus of the mature protein. To investigate the structural requirements of the COOH terminus of the nascent protein for PI-G tailing and anchoring to the plasma membrane, we have transfected COS cells with wild type and mutant forms of cDNA encoding human prepro-PLAP. Utilizing a series of COOH-terminal deletion mutants of prepro-PLAP, it was found that to be PI-G-tailed the newly synthesized protein must possess an uncharged, predominantly hydrophobic amino acid sequence of a minimal length in the COOH-terminal peptide. While forms of prepro-PLAP with 17 consecutive hydrophobic residues in the terminal sequence yielded PI-G-tailed and membrane-bound products, prepro-PLAP mutants with 13 or fewer of such residues yielded hydrophilic proteins that were no longer PI-G-tailed but efficiently secreted into the medium. Studies using cassette mutants demonstrated that the precise amino sequence of the COOH-terminal region could be altered as long as minimal hydrophobicity and length was maintained.

Full Text

Duke Authors

Cited Authors

  • Berger, J; Howard, AD; Brink, L; Gerber, L; Hauber, J; Cullen, BR; Udenfriend, S

Published Date

  • July 15, 1988

Published In

Volume / Issue

  • 263 / 20

Start / End Page

  • 10016 - 10021

PubMed ID

  • 3290206

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States