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Title: Structure of the Integral Membrane Protein CAAX Protease Ste24p

Abstract

Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a -factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.

Authors:
 [1];  [1];  [2];  [2];  [2];  [3];  [3];  [4];  [1];  [2]
  1. Membrane Protein Structural Biology Consortium (United States); Univ. of Virginia, Charlottesville, VA (United States)
  2. Membrane Protein Structural Biology Consortium (United States); Univ. of Rochester School of Medicine and Dentistry, Rochester, NY (United States)
  3. Membrane Protein Structural Biology Consortium (United States); Hauptman-Woodward Inst., Buffalo, NY (United States)
  4. Membrane Protein Structural Biology Consortium (United States); Hauptman-Woodward Inst., Buffalo, NY (United States); State Univ. of New York, Buffalo, NY (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health, New York, NY (United States)
OSTI Identifier:
1072772
Resource Type:
Journal Article
Journal Name:
Science
Additional Journal Information:
Journal Volume: 339; Journal Issue: 03, 2013; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Pryor Jr., Edward E., Horanyi, Peter S., Clark, Kathleen M., Fedoriw, Nadia, Connelly, Sara M., Koszelak-Rosenblum, Mary, Zhu, Guangyu, Malkowski, Michael G., Wiener, Michael C., and Dumont, Mark E. Structure of the Integral Membrane Protein CAAX Protease Ste24p. United States: N. p., 2012. Web. doi:10.1126/science.1232048.
Pryor Jr., Edward E., Horanyi, Peter S., Clark, Kathleen M., Fedoriw, Nadia, Connelly, Sara M., Koszelak-Rosenblum, Mary, Zhu, Guangyu, Malkowski, Michael G., Wiener, Michael C., & Dumont, Mark E. Structure of the Integral Membrane Protein CAAX Protease Ste24p. United States. doi:10.1126/science.1232048.
Pryor Jr., Edward E., Horanyi, Peter S., Clark, Kathleen M., Fedoriw, Nadia, Connelly, Sara M., Koszelak-Rosenblum, Mary, Zhu, Guangyu, Malkowski, Michael G., Wiener, Michael C., and Dumont, Mark E. Fri . "Structure of the Integral Membrane Protein CAAX Protease Ste24p". United States. doi:10.1126/science.1232048.
@article{osti_1072772,
title = {Structure of the Integral Membrane Protein CAAX Protease Ste24p},
author = {Pryor Jr., Edward E. and Horanyi, Peter S. and Clark, Kathleen M. and Fedoriw, Nadia and Connelly, Sara M. and Koszelak-Rosenblum, Mary and Zhu, Guangyu and Malkowski, Michael G. and Wiener, Michael C. and Dumont, Mark E.},
abstractNote = {Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a -factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.},
doi = {10.1126/science.1232048},
journal = {Science},
issn = {0036-8075},
number = 03, 2013,
volume = 339,
place = {United States},
year = {2012},
month = {10}
}