title: The exomer cargo adaptor features a flexible hinge domain.
abstract: Exomer is a cargo adaptor that mediates the sorting of specific plasma membrane proteins into vesicles at the trans-Golgi network. Cargo adaptors must bind to multiple partners, including their cargo, regulatory proteins, and the membrane surface. During biogenesis of a vesicle, the membrane makes a transition from a relatively flat surface to one of high curvature, requiring cargo adaptors to somehow maintain protein-protein and protein-membrane interactions on a changing membrane environment. Here, we present the crystal structure of a tetrameric Chs5/Bch1 exomer complex and use small-angle X-ray scattering to demonstrate its flexibility in solution. The structural data suggest that the complex flexes primarily around the dimeric N-terminal domain of the Chs5 subunits, which adopts a noncanonical β sandwich fold. We propose that this flexible hinge domain enables exomer to maintain interactions in the context of a dynamic membrane environment.
authors: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
authors: Brian C
authors: BC
authors: Richardson
authors: J Christopher
authors: JC
authors: Fromme
mesh_terms: D001665:Binding Sites; D002687:Chitin Synthase / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D021601:trans-Golgi Network / Q000737:chemistry
chemical_list: D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C491360:CHS5 protein, S cerevisiae; D002687:Chitin Synthase
references: J Cell Biol. 2006 Sep 25;174(7):973-83
references: 17000877
references: Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
references: 20057044
references: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14108-13
references: 15377783
references: Eukaryot Cell. 2003 Aug;2(4):821-5
references: 12912901
references: Mol Biol Cell. 2006 Oct;17(10):4157-66
references: 16855022
references: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
references: 20383002
references: Nat Struct Biol. 1998 Feb;5(2):110-4
references: 9461075
references: EMBO J. 2012 Nov 5;31(21):4191-203
references: 23000721
references: Curr Opin Struct Biol. 2002 Dec;12(6):794-801
references: 12504685
references: Biophys J. 2006 Mar 1;90(5):1583-93
references: 16361336
references: Cell. 2012 Feb 3;148(3):530-42
references: 22304919
references: Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6408-12
references: 1631136
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
references: 20457744
references: Protein Eng. 2001 Jan;14(1):1-6
references: 11287673
references: Nature. 2008 Dec 18;456(7224):976-979
references: 19140243
references: Mol Cell Biol. 1997 May;17(5):2485-96
references: 9111317
references: Methods Enzymol. 1997;276:307-26
references: 27754618
references: J Cell Biol. 1991 Aug;114(4):671-9
references: 1907974
references: Mol Biol Cell. 2009 Dec;20(23):4985-96
references: 19812245
references: Science. 1993 Mar 5;259(5100):1466-8
references: 8451644
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W610-4
references: 15215461
references: Cell. 1998 Apr 17;93(2):263-75
references: 9568718
references: Phys Rev Lett. 1996 Aug 26;77(9):1905-1908
references: 10063201
references: Curr Opin Cell Biol. 2001 Aug;13(4):444-53
references: 11454451
references: Nat Rev Mol Cell Biol. 2008 Apr;9(4):273-84
references: 18354421
references: Cell. 1991 Oct 18;67(2):239-53
references: 1680566
references: Annu Rev Cell Dev Biol. 2004;20:153-91
references: 15473838
references: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references: 20124702
references: Biochem Biophys Res Commun. 2001 Jun 22;284(4):1083-9
references: 11409905
references: Mol Biol Cell. 2012 Nov;23(22):4402-15
references: 23015758
references: PLoS One. 2012;7(10):e46386
references: 23056294
references: Proc Natl Acad Sci U S A. 2006 May 23;103(21):8060-5
references: 16690741
references: Nature. 2002 Sep 19;419(6904):271-7
references: 12239560
references: Cell. 2006 Dec 1;127(5):941-54
references: 17129781
references: EMBO J. 2006 Mar 8;25(5):943-54
references: 16498409
references: J Appl Crystallogr. 2009 Apr 1;42(Pt 2):342-346
references: 27630371
references: Cell. 2010 Jun 25;141(7):1220-9
references: 20603002
references: Dev Cell. 2007 Nov;13(5):635-645
references: 17981133
references: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references: 15034147
references: Nature. 2007 Oct 25;449(7165):1063-7
references: 17891154
references: Cell. 2002 May 17;109(4):523-35
references: 12086608