Atomic-Resolution Structures of the APC/C Subunits Apc4 and the Apc5 N-Terminal Domain

Journal of Molecular Biology
Nora B CroninDavid Barford

Abstract

Many essential biological processes are mediated by complex molecular machines comprising multiple subunits. Knowledge on the architecture of individual subunits and their positions within the overall multimeric complex is key to understanding the molecular mechanisms of macromolecular assemblies. The anaphase-promoting complex/cyclosome (APC/C) is a large multisubunit complex that regulates cell cycle progression by ubiquitinating cell cycle proteins for proteolysis by the proteasome. The holo-complex is composed of 15 different proteins that assemble to generate a complex of 20 subunits. Here, we describe the crystal structures of Apc4 and the N-terminal domain of Apc5 (Apc5(N)). Apc4 comprises a WD40 domain split by a long α-helical domain, whereas Apc5(N) has an α-helical fold. In a separate study, we had fitted these atomic models to a 3.6-Å-resolution cryo-electron microscopy map of the APC/C. We describe how, in the context of the APC/C, regions of Apc4 disordered in the crystal assume order through contacts to Apc5, whereas Apc5(N) shows small conformational changes relative to its crystal structure. We discuss the complementary approaches of high-resolution electron microscopy and protein crystallography to the structu...Continue Reading

References

Jan 10, 1991·Nature·M GlotzerM W Kirschner
Jan 1, 1993·Protein Engineering·G J Barton
May 4, 2000·Molecular Biology of the Cell·E R KramerJ M Peters
Jun 28, 2000·The Journal of Cell Biology·A D Rudner, A W Murray
Jul 11, 2000·Molecular Biology of the Cell·J D LeversonT Hunter
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·M GmachlJ M Peters
Sep 20, 2001·Genes & Development·C M PflegerM W Kirschner
Apr 19, 2002·Nature·Ning ZhengNikola P Pavletich
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Dec 6, 2003·The EMBO Journal·Claudine KraftJan-Michael Peters
Dec 9, 2003·Trends in Biochemical Sciences·Luca D D'Andrea, Lynne Regan
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 15, 2005·Current Biology : CB·Christopher W CarrollDavid O Morgan
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Engin OzkanJohann Deisenhofer
Feb 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Esther EytanAvram Hershko
Jul 18, 2006·Nucleic Acids Research·Andreas BiegertAndrei N Lupas
Apr 25, 2007·Nucleic Acids Research·Ian W DavisDavid C Richardson
Jul 31, 2007·Protein Science : a Publication of the Protein Society·Ciarán N CroninJoe Rogers
Apr 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Judith A J SteenMarc W Kirschner
Sep 27, 2008·Bioinformatics·L HolmA Schenkel
Dec 19, 2008·The Journal of Biological Chemistry·Dohyun HanYoungsoo Kim
Feb 28, 2009·Nature Protocols·Lawrence A Kelley, Michael J E Sternberg
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Aug 12, 2009·Nature Structural & Molecular Biology·Jing WangBrenda A Schulman
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
May 29, 2010·Nucleic Acids Research·Dina Schneidman-DuhovnyAndrej Sali
Aug 25, 2010·The Journal of Cell Biology·Wouter van ZonRob M F Wolthuis
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Apr 12, 2011·Seminars in Cell & Developmental Biology·Hermann-Josef Meyer, Michael Rape
Jun 3, 2011·Nature Reviews. Molecular Cell Biology·Jonathon Pines
Oct 4, 2011·Journal of Structural Biology·Zheng YangThomas E Ferrin
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·David Barford

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Methods Mentioned

BETA
ubiquitination
electron microscopy
X-ray
NMR
PCR
size-exclusion chromatography
gel-filtration

Software Mentioned

PHENIX
PyMOL
REFMAC
OnD
CRF
PRIMUS
PARROT
Xds
CCP4
SHARP

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