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3t9k

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Crystal Structure of ACAP1 C-portion mutant S554D fused with integrin beta1 peptide

Structural highlights

3t9k is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ITB1_HUMAN Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. Isoform beta-1B interferes with isoform beta-1A resulting in a dominant negative effect on cell adhesion and migration (in vitro). In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. When associated with alpha-7/beta-1 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and GNB2L1/RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis.^[1] ^[2] ^[3] ACAP1_HUMAN GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Coat complexes sort protein cargoes into vesicular transport pathways. An emerging class of coat components has been the GAPs (GTPase activating proteins) that act on the ARF (ADP-Ribosylation factor) family of small GTPases. ACAP1 (ArfGAP with Coil coil, Ankyrin repeat, and PH domain protein 1) is an ARF6 GAP that also acts as a key component of a recently defined clathrin complex for endocytic recycling. Phosphorylation by Akt has been shown to enhance cargo binding by ACAP1 in explaining how integrin recycling is an example of regulated transport. We now shed further mechanistic insights into how this regulation is achieved at the level of cargo binding by ACAP1. We initially define a critical sequence in the cytoplasmic domain of integrin beta1 recognized by ACAP1, and show that this sequence acts as a recycling sorting signal. We then pursue a combination of structural, modeling and functional studies, which suggest that phosphorylation of ACAP1 relieves a localized mechanism of auto-inhibition in regulating cargo binding. Thus, we have elucidated a key regulatory juncture that controls integrin recycling, and also advanced the understanding of how regulated cargo binding can lead to regulated transport.

Mechanistic insights into regulated cargo binding by ACAP1.,Bai M, Pang X, Lou J, Zhou Q, Zhang K, Ma J, Li J, Sun F, Hsu V J Biol Chem. 2012 May 29. PMID:22645133^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Balzac F, Retta SF, Albini A, Melchiorri A, Koteliansky VE, Geuna M, Silengo L, Tarone G. Expression of beta 1B integrin isoform in CHO cells results in a dominant negative effect on cell adhesion and motility. J Cell Biol. 1994 Oct;127(2):557-65. PMID:7523423
↑ Chuang NN, Huang CC. Interaction of integrin beta1 with cytokeratin 1 in neuroblastoma NMB7 cells. Biochem Soc Trans. 2007 Nov;35(Pt 5):1292-4. PMID:17956333 doi:10.1042/BST0351292
↑ Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H, Grosse R, Kitzing T, Rantala JK, Kallioniemi O, Fassler R, Kallio M, Ivaska J. Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell. 2008 Sep;15(3):371-85. PMID:18804435 doi:http://dx.doi.org/S1534-5807(08)00324-9
↑ Jackson TR, Brown FD, Nie Z, Miura K, Foroni L, Sun J, Hsu VW, Donaldson JG, Randazzo PA. ACAPs are arf6 GTPase-activating proteins that function in the cell periphery. J Cell Biol. 2000 Oct 30;151(3):627-38. PMID:11062263
↑ Li J, Ballif BA, Powelka AM, Dai J, Gygi SP, Hsu VW. Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration. Dev Cell. 2005 Nov;9(5):663-73. PMID:16256741 doi:http://dx.doi.org/S1534-5807(05)00374-6
↑ Ma Z, Nie Z, Luo R, Casanova JE, Ravichandran KS. Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP. Curr Biol. 2007 Apr 17;17(8):722-7. Epub 2007 Mar 29. PMID:17398097 doi:http://dx.doi.org/S0960-9822(07)01115-3
↑ Li J, Peters PJ, Bai M, Dai J, Bos E, Kirchhausen T, Kandror KV, Hsu VW. An ACAP1-containing clathrin coat complex for endocytic recycling. J Cell Biol. 2007 Jul 30;178(3):453-64. PMID:17664335 doi:http://dx.doi.org/jcb.200608033
↑ Bai M, Pang X, Lou J, Zhou Q, Zhang K, Ma J, Li J, Sun F, Hsu V. Mechanistic insights into regulated cargo binding by ACAP1. J Biol Chem. 2012 May 29. PMID:22645133 doi:10.1074/jbc.M112.378810
↑ Bai M, Pang X, Lou J, Zhou Q, Zhang K, Ma J, Li J, Sun F, Hsu V. Mechanistic insights into regulated cargo binding by ACAP1. J Biol Chem. 2012 May 29. PMID:22645133 doi:10.1074/jbc.M112.378810

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3t9k"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of ACAP1 C-portion mutant S554D fused with integrin beta1 peptide==
-<StructureSection load='3t9k' size='340' side='right' caption='[[3t9k]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='3t9k' size='340' side='right'caption='[[3t9k]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3t9k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T9K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3t9k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T9K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3t9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t9k OCA], [http://pdbe.org/3t9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t9k RCSB], [http://www.ebi.ac.uk/pdbsum/3t9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t9k ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3t9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t9k OCA], [https://pdbe.org/3t9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t9k RCSB], [https://www.ebi.ac.uk/pdbsum/3t9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t9k ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ACAP1_HUMAN ACAP1_HUMAN]] GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.<ref>PMID:11062263</ref> <ref>PMID:16256741</ref> <ref>PMID:17398097</ref> <ref>PMID:17664335</ref> <ref>PMID:22645133</ref>
+[https://www.uniprot.org/uniprot/ITB1_HUMAN ITB1_HUMAN] Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. Isoform beta-1B interferes with isoform beta-1A resulting in a dominant negative effect on cell adhesion and migration (in vitro). In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. When associated with alpha-7/beta-1 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and GNB2L1/RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis.<ref>PMID:7523423</ref> <ref>PMID:17956333</ref> <ref>PMID:18804435</ref> [https://www.uniprot.org/uniprot/ACAP1_HUMAN ACAP1_HUMAN] GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.<ref>PMID:11062263</ref> <ref>PMID:16256741</ref> <ref>PMID:17398097</ref> <ref>PMID:17664335</ref> <ref>PMID:22645133</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Ma, J]]
+[[Category: Homo sapiens]]
-[[Category: Pang, X]]
+[[Category: Large Structures]]
-[[Category: Sun, F]]
+[[Category: Ma J]]
-[[Category: Zhang, K]]
+[[Category: Pang X]]
-[[Category: Zhou, Q]]
+[[Category: Sun F]]
-[[Category: Ank repeat]]
+[[Category: Zhang K]]
-[[Category: Arfgap domain]]
+[[Category: Zhou Q]]
-[[Category: Protein transport]]
-[[Category: Zinc-binding module]]

3t9k

From Proteopedia

Current revision

Crystal Structure of ACAP1 C-portion mutant S554D fused with integrin beta1 peptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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