4gxb

From Proteopedia

(Difference between revisions)

Revision as of 04:32, 5 August 2016

Structure of the SNX17 atypical FERM domain bound to the NPxY motif of P-selectin

Structural highlights

4gxb is a 2 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3lui, 3fog, 1hes
Gene:	SNX17 (HUMAN), Selp (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SNX17_HUMAN] Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [LYAM3_MOUSE] Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.^[7]

Publication Abstract from PubMed

Transit of proteins through the endosomal organelle following endocytosis is critical for regulating the homeostasis of cell-surface proteins and controlling signal transduction pathways. However, the mechanisms that control these membrane-transport processes are poorly understood. The Phox-homology (PX) domain-containing proteins sorting nexin (SNX) 17, SNX27, and SNX31 have emerged recently as key regulators of endosomal recycling and bind conserved Asn-Pro-Xaa-Tyr-sorting signals in transmembrane cargos via an atypical band, 4.1/ezrin/radixin/moesin (FERM) domain. Here we present the crystal structure of the SNX17 FERM domain bound to the sorting motif of the P-selectin adhesion protein, revealing both the architecture of the atypical FERM domain and the molecular basis for recognition of these essential sorting sequences. We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins.

Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.,Ghai R, Bugarcic A, Liu H, Norwood SJ, Skeldal S, Coulson EJ, Li SS, Teasdale RD, Collins BM Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E643-52. doi:, 10.1073/pnas.1216229110. Epub 2013 Feb 4. PMID:23382219^[8]

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

References

↑ Williams R, Schluter T, Roberts MS, Knauth P, Bohnensack R, Cutler DF. Sorting nexin 17 accelerates internalization yet retards degradation of P-selectin. Mol Biol Cell. 2004 Jul;15(7):3095-105. Epub 2004 Apr 30. PMID:15121882 doi:10.1091/mbc.E04-02-0143
↑ Knauth P, Schluter T, Czubayko M, Kirsch C, Florian V, Schreckenberger S, Hahn H, Bohnensack R. Functions of sorting nexin 17 domains and recognition motif for P-selectin trafficking. J Mol Biol. 2005 Apr 8;347(4):813-25. PMID:15769472 doi:S0022-2836(05)00144-0
↑ Czubayko M, Knauth P, Schluter T, Florian V, Bohnensack R. Sorting nexin 17, a non-self-assembling and a PtdIns(3)P high class affinity protein, interacts with the cerebral cavernous malformation related protein KRIT1. Biochem Biophys Res Commun. 2006 Jul 7;345(3):1264-72. Epub 2006 May 2. PMID:16712798 doi:10.1016/j.bbrc.2006.04.129
↑ Donoso M, Cancino J, Lee J, van Kerkhof P, Retamal C, Bu G, Gonzalez A, Caceres A, Marzolo MP. Polarized traffic of LRP1 involves AP1B and SNX17 operating on Y-dependent sorting motifs in different pathways. Mol Biol Cell. 2009 Jan;20(1):481-97. doi: 10.1091/mbc.E08-08-0805. Epub 2008 Nov, 12. PMID:19005208 doi:10.1091/mbc.E08-08-0805
↑ Steinberg F, Heesom KJ, Bass MD, Cullen PJ. SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways. J Cell Biol. 2012 Apr 16;197(2):219-30. doi: 10.1083/jcb.201111121. Epub 2012 Apr, 9. PMID:22492727 doi:10.1083/jcb.201111121
↑ Ghai R, Mobli M, Norwood SJ, Bugarcic A, Teasdale RD, King GF, Collins BM. Phox homology band 4.1/ezrin/radixin/moesin-like proteins function as molecular scaffolds that interact with cargo receptors and Ras GTPases. Proc Natl Acad Sci U S A. 2011 Apr 21. PMID:21512128 doi:10.1073/pnas.1017110108
↑ Hirata T, Furie BC, Furie B. P-, E-, and L-selectin mediate migration of activated CD8+ T lymphocytes into inflamed skin. J Immunol. 2002 Oct 15;169(8):4307-13. PMID:12370362
↑ Ghai R, Bugarcic A, Liu H, Norwood SJ, Skeldal S, Coulson EJ, Li SS, Teasdale RD, Collins BM. Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E643-52. doi:, 10.1073/pnas.1216229110. Epub 2013 Feb 4. PMID:23382219 doi:http://dx.doi.org/10.1073/pnas.1216229110

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gxb"

@@ Line 1: / Line 1: @@
 ==Structure of the SNX17 atypical FERM domain bound to the NPxY motif of P-selectin==
 <StructureSection load='4gxb' size='340' side='right' caption='[[4gxb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4gxb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GXB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4gxb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GXB FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lui|3lui]], [[3fog|3fog]], [[1hes|1hes]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNX17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), Selp ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNX17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Selp ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4gxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gxb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gxb RCSB], [http://www.ebi.ac.uk/pdbsum/4gxb 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=4gxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gxb OCA], [http://pdbe.org/4gxb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gxb RCSB], [http://www.ebi.ac.uk/pdbsum/4gxb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gxb ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SNX17_HUMAN SNX17_HUMAN]] Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).<ref>PMID:15121882</ref> <ref>PMID:15769472</ref> <ref>PMID:16712798</ref> <ref>PMID:19005208</ref> <ref>PMID:22492727</ref> <ref>PMID:21512128</ref>
+[[http://www.uniprot.org/uniprot/SNX17_HUMAN SNX17_HUMAN]] Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).<ref>PMID:15121882</ref> <ref>PMID:15769472</ref> <ref>PMID:16712798</ref> <ref>PMID:19005208</ref> <ref>PMID:22492727</ref> <ref>PMID:21512128</ref>  [[http://www.uniprot.org/uniprot/LYAM3_MOUSE LYAM3_MOUSE]] Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.<ref>PMID:12370362</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4gxb" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Bugarcic, A]]
 [[Category: Collins, B M]]

4gxb

From Proteopedia

Revision as of 04:32, 5 August 2016

Structure of the SNX17 atypical FERM domain bound to the NPxY motif of P-selectin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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