3t9k: Difference between revisions

Revision as of 02:10, 5 August 2016

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

Structural highlights

3t9k is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	SO4, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

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

References

↑ 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:https://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:https://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:https://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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/S1534-5807(05)00374-6

[3] 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:https://dx.doi.org/S0960-9822(07)01115-3

[4] 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:https://dx.doi.org/jcb.200608033

[5] 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

[6] 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

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@@ 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=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3t9k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. 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 [http://en.wikipedia.org/wiki/Human Human]. 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>
 </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>
-<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://www.rcsb.org/pdb/explore.do?structureId=3t9k RCSB], [http://www.ebi.ac.uk/pdbsum/3t9k PDBsum]</span></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>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3t9k" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Synthetic construct]]
+[[Category: Human]]
 [[Category: Ma, J]]
 [[Category: Pang, X]]

3t9k: Difference between revisions

Revision as of 02:10, 5 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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