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5l81

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Crystal structure of the PH domain of murine kindlin-3

Structural highlights

5l81 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.23Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

URP2_MOUSE Plays a central role in cell adhesion in hematopoietic cells (By similarity). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (PubMed:18278053). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234461). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (PubMed:18278053).[UniProtKB:Q86UX7]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Kindlins co-activate integrins alongside talin. They possess, like talin, a FERM domain comprising F0-F3 subdomains, but with a pleckstrin homology (PH) domain inserted in the F2 subdomain that enables membrane association. We present the crystal structure of murine kindlin-3 PH domain determined at 2.23A resolution and characterise its lipid binding using biophysical and computational approaches. Molecular dynamics (MD) simulations suggest flexibility in the PH domain loops connecting beta-strands forming the putative phosphatidylinositol phosphate (PtdInsP) binding site. Simulations with PtdInsP-containing bilayers reveal that the PH domain associates with PtdInsP molecules mainly via the positively charged surface presented by the beta1-beta2 loop and that it binds with somewhat higher affinity to PtdIns(3,4,5)P3 compared to PtdIns(4,5)P2 Surface plasmon resonance (SPR) with lipid headgroups immobilised and the PH domain as analyte indicate affinities of 300 muM for PtdIns(3,4,5)P3 and 1mM for PtdIns(4,5)P2 In contrast, SPR studies with immobilised PH domain and lipid nanodiscs as analyte show affinities of 0.40 microM for PtdIns(3,4,5)P3 and no affinity for PtdIns(4,5)P2 when the inositol phosphate constitutes 5% of the total lipids (~5 molecules per nanodisc). Reducing the PtdIns(3,4,5)P3 composition to 1% abolishes nanodisc binding to the PH domain, as does site-directed mutagenesis of two lysines within the beta1-beta2 loop. Binding of PtdIns(3,4,5)P3 by a canonical PH domain, Grp1, is not similarly influenced by SPR experimental design. These data suggest a role for PtdIns(3,4,5)P3 clustering in the binding of some PH domains and not others, highlighting the importance lipid mobility and clustering for the biophysical assessment of protein-membrane interactions.

Structure and lipid binding properties of the kindlin-3 pleckstrin homology domain.,Ni T, Kalli A, Naughton F, Yates L, Naneh O, Kozorog M, Anderluh G, Sansom M, Gilbert R Biochem J. 2016 Dec 14. pii: BCJ20160791. PMID:27974389^[4]

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

References

↑ Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med. 2008 Mar;14(3):325-30. doi: 10.1038/nm1722. Epub 2008 Feb 17. PMID:18278053 doi:http://dx.doi.org/10.1038/nm1722
↑ Kruger M, Moser M, Ussar S, Thievessen I, Luber CA, Forner F, Schmidt S, Zanivan S, Fassler R, Mann M. SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell. 2008 Jul 25;134(2):353-64. doi: 10.1016/j.cell.2008.05.033. PMID:18662549 doi:http://dx.doi.org/10.1016/j.cell.2008.05.033
↑ Moser M, Bauer M, Schmid S, Ruppert R, Schmidt S, Sixt M, Wang HV, Sperandio M, Fassler R. Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat Med. 2009 Mar;15(3):300-5. doi: 10.1038/nm.1921. Epub 2009 Feb 22. PMID:19234461 doi:http://dx.doi.org/10.1038/nm.1921
↑ Ni T, Kalli A, Naughton F, Yates L, Naneh O, Kozorog M, Anderluh G, Sansom M, Gilbert R. Structure and lipid binding properties of the kindlin-3 pleckstrin homology domain. Biochem J. 2016 Dec 14. pii: BCJ20160791. PMID:27974389 doi:http://dx.doi.org/10.1042/BCJ20160791

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/5l81"

Categories: Large Structures | Mus musculus | Gilbert RJC | Harlos K | Ni T

@@ Line 3: / Line 3: @@
 <StructureSection load='5l81' size='340' side='right'caption='[[5l81]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l81]] is a 2 chain structure with sequence from [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=5L81 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L81 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l81]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L81 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L81 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.23&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fermt3, Kind3, Urp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=5l81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l81 OCA], [http://pdbe.org/5l81 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l81 RCSB], [http://www.ebi.ac.uk/pdbsum/5l81 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l81 ProSAT]</span></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=5l81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l81 OCA], [https://pdbe.org/5l81 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l81 RCSB], [https://www.ebi.ac.uk/pdbsum/5l81 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l81 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/URP2_MOUSE URP2_MOUSE]] Plays a central role in cell adhesion in hematopoietic cells (By similarity). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (PubMed:18278053). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234461). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (PubMed:18278053).[UniProtKB:Q86UX7]<ref>PMID:18278053</ref> <ref>PMID:18662549</ref> <ref>PMID:19234461</ref>
+[https://www.uniprot.org/uniprot/URP2_MOUSE URP2_MOUSE] Plays a central role in cell adhesion in hematopoietic cells (By similarity). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (PubMed:18278053). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234461). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (PubMed:18278053).[UniProtKB:Q86UX7]<ref>PMID:18278053</ref> <ref>PMID:18662549</ref> <ref>PMID:19234461</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Gilbert, R J.C]]
+[[Category: Gilbert RJC]]
-[[Category: Harlos, K]]
+[[Category: Harlos K]]
-[[Category: Ni, T]]
+[[Category: Ni T]]
-[[Category: Integrin activation]]
-[[Category: Membrane binding]]
-[[Category: Pleckstrin homology domain]]
-[[Category: Signaling protein]]

5l81

From Proteopedia

Current revision

Crystal structure of the PH domain of murine kindlin-3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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