title: Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain.
abstract: FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their μ homology domains (μHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity μHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal μHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 μHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the μHD, which is distinct from those of other distantly related μHD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the μHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in μHD binding.
authors.affiliation: Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.|RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimada
authors.affiliation: Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohda
mesh_terms: D033965:Adaptor Protein Complex alpha Subunits / Q000737:chemistry / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001665:Binding Sites; D002151:Calorimetry; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D033965:Adaptor Protein Complex alpha Subunits; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D002352:Carrier Proteins; C486206:EPS15 protein, human; D008024:Ligands; D008565:Membrane Proteins; C523897:SGIP1 protein, human
references.citation: Cell. 1999 Jun 11;97(6):805-15
references.pmid: 10380931
references.citation: Int J Biochem Cell Biol. 1999 Aug;31(8):805-9
references.pmid: 10481267
references.citation: EMBO J. 2000 Aug 15;19(16):4216-27
references.pmid: 10944104
references.citation: Nat Struct Biol. 2000 Nov;7(11):1018-22
references.pmid: 11062555
references.citation: Structure. 2002 Jun;10(6):797-809
references.pmid: 12057195
references.citation: Bioinformatics. 2002;18 Suppl 1:S71-7
references.pmid: 12169533
references.citation: J Biol Chem. 2004 Oct 29;279(44):46191-203
references.pmid: 15292237
references.citation: EMBO J. 2004 Nov 10;23(22):4371-83
references.pmid: 15496985
references.citation: Biopolymers. 2005;80(2-3):179-85
references.pmid: 15700296
references.citation: Endocrinology. 2005 Sep;146(9):3757-64
references.pmid: 15919751
references.citation: Dev Cell. 2005 Dec;9(6):791-804
references.pmid: 16326391
references.citation: J Cell Biol. 2006 Jan 16;172(2):269-79
references.pmid: 16418535
references.citation: Dev Cell. 2006 Mar;10(3):329-42
references.pmid: 16516836
references.citation: PLoS Biol. 2006 Sep;4(9):e262
references.pmid: 16903783
references.citation: Protein Sci. 2007 Jan;16(1):30-42
references.pmid: 17192587
references.citation: Cell. 2007 May 18;129(4):761-72
references.pmid: 17512409
references.citation: Structure. 2007 Jul;15(7):839-52
references.pmid: 17540576
references.citation: J Biol Chem. 2007 Sep 7;282(36):26481-9
references.pmid: 17626015
references.citation: Nature. 2007 Aug 23;448(7156):883-8
references.pmid: 17713526
references.citation: J Biol Chem. 2008 Feb 22;283(8):5099-109
references.pmid: 17986441
references.citation: EMBO J. 2008 Feb 6;27(3):558-69
references.pmid: 18200045
references.citation: Cell. 2008 Mar 7;132(5):807-17
references.pmid: 18329367
references.citation: EMBO J. 2009 Oct 21;28(20):3103-16
references.pmid: 19713939
references.citation: Cell Commun Signal. 2009 Oct 08;7:24
references.pmid: 19814798
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references.pmid: 20124702
references.citation: Dev Cell. 2010 Mar 16;18(3):425-36
references.pmid: 20230749
references.citation: Science. 2010 Jun 4;328(5983):1281-4
references.pmid: 20448150
references.citation: Int J Obes (Lond). 2012 Feb;36(2):201-6
references.pmid: 21407171
references.citation: Genes Cells. 2011 Aug;16(8):868-78
references.pmid: 21762413
references.citation: Nat Rev Mol Cell Biol. 2011 Jul 22;12(8):517-33
references.pmid: 21779028
references.citation: Mol Biol Cell. 2012 Apr;23(7):1330-42
references.pmid: 22323290
references.citation: Nat Cell Biol. 2012 Apr 08;14(5):488-501
references.pmid: 22484487
references.citation: Anal Chem. 2012 Jun 5;84(11):5066-73
references.pmid: 22530732
references.citation: Cell. 2012 Aug 3;150(3):495-507
references.pmid: 22863004
references.citation: J Biol Chem. 2013 Mar 29;288(13):9563-71
references.pmid: 23404500
references.citation: J Mol Biol. 2013 Jun 26;425(12):2100-32
references.pmid: 23507311
references.citation: Elife. 2014 Oct 10;3:null
references.pmid: 25303365
references.citation: Elife. 2014 Oct 10;3:null
references.pmid: 25303366
references.citation: Acta Crystallogr D Biol Crystallogr. 2015 Jun;71(Pt 6):1328-34
references.pmid: 26057672
references.citation: Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14242-7
references.pmid: 26578768
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: J Cell Biol. 1995 Dec;131(6 Pt 2):1831-8
references.pmid: 8557749
references.citation: J Biol Chem. 1996 May 17;271(20):12111-6
references.pmid: 8662627
references.citation: J Biol Chem. 1998 Jan 23;273(4):1847-50
references.pmid: 9442014
references.citation: J Biol Chem. 1998 Jan 30;273(5):3003-12
references.pmid: 9446614
references.citation: Science. 1998 Nov 13;282(5392):1327-32
references.pmid: 9812899