PMID: 9636145Jun 24, 1998Paper

A model for the structure of the P domains in the subtilisin-like prohormone convertases

Proceedings of the National Academy of Sciences of the United States of America
G LipkindD F Steiner

Abstract

The proprotein convertases are a family of at least seven calcium-dependent endoproteases that process a wide variety of precursor proteins in the secretory pathway. All members of this family possess an N-terminal proregion, a subtilisin-like catalytic module, and an additional downstream well-conserved region of approximately 150 amino acid residues, the P domain, which is not found in any other subtilase. The pro and catalytic domains cannot be expressed in the absence of the P domains; their thermodynamic instability may be attributable to the presence of large numbers of negatively charged Glu and Asp side chains in the substrate binding region for recognition of multibasic residue cleavage sites. Based on secondary structure predictions, we here propose that the P domains consist of 8-stranded beta-barrels with well-organized inner hydrophobic cores, and therefore are independently folded components of the proprotein convertases. We hypothesize further that the P domains are integrated through strong hydrophobic interactions with the catalytic domains, conferring structural stability and regulating the properties and activity of the convertases. A molecular model of these interdomain interactions is proposed in this report.

References

Jan 1, 1978·Annual Review of Biochemistry·P Y Chou, G D Fasman
Jun 17, 1976·Nature·M Levitt, C Chothia
Jan 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S P SmeekensD F Steiner
Nov 1, 1990·Molecular Biology Reports·W J van de VenR J Siezen
Mar 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R S FullerJ Thorner
Oct 14, 1988·Biochemical and Biophysical Research Communications·K MizunoH Matsuo
Jun 20, 1987·Journal of Molecular Biology·M J ZvelebilM J Sternberg
Nov 26, 1987·Biochimica Et Biophysica Acta·R W WilliamsS Loughran
Jan 15, 1974·Biochemistry·P Y Chou, G D Fasman
Oct 15, 1983·Journal of Molecular Biology·G WistowT Blundell
Jan 1, 1981·Advances in Protein Chemistry·J S Richardson
Nov 1, 1993·Protein Science : a Publication of the Protein Society·J BajorathA Aruffo
Jan 20, 1993·Journal of Molecular Biology·S A BennerD Gerloff
Jun 2, 1995·The Journal of Biological Chemistry·G LipkindD F Steiner
May 1, 1994·Protein Science : a Publication of the Protein Society·L YoungD G Covell
Jun 1, 1993·Protein Science : a Publication of the Protein Society·T L Blundell, M S Johnson
Aug 3, 1993·Biochemistry·E T Harper, G D Rose
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Mar 15, 1996·The Biochemical Journal·A BruzzanitiM T Gillespie
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·N G SeidahR Day
Jan 1, 1997·Protein Science : a Publication of the Protein Society·C J TsaiR Nussinov
Mar 1, 1997·Protein Science : a Publication of the Protein Society·R J Siezen, J A Leunissen
Feb 14, 1998·The Journal of Biological Chemistry·X ZhuI Lindberg
Jun 6, 1998·The Journal of Biological Chemistry·A ZhouD F Steiner

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Citations

Jun 8, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·C Thacker, A M Rose
Nov 19, 2003·Archives of Biochemistry and Biophysics·Saule NaureckieneBrendan Bingham
Apr 23, 2004·Trends in Biochemical Sciences·Nathan C Rockwell, Jeremy W Thorner
Jul 4, 2002·Journal of Molecular Biology·Michael A TangreaJohn Orban
Jan 5, 2000·Applied and Environmental Microbiology·R JalvingP J Schaap
May 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kazuya UedaDonald F Steiner
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·N G SeidahM Marcinkiewicz
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nabil G SeidahMichel Chretien
Apr 22, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Sylvia NelsenJan L Christian
Jul 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Neil A TaylorJohn W M Creemers
Jul 20, 1999·The Journal of Biological Chemistry·A ZhouD F Steiner
Nov 28, 2001·The Journal of Biological Chemistry·Martin FugèreRobert Day
Aug 4, 2021·Journal of Medicinal Chemistry·Essam Eldin A OsmanNouri Neamati

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