2xac: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 3: Line 3:
<StructureSection load='2xac' size='340' side='right'caption='[[2xac]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
<StructureSection load='2xac' size='340' side='right'caption='[[2xac]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2xac]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XAC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XAC FirstGlance]. <br>
<table><tr><td colspan='2'>[[2xac]] is a 4 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=2XAC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XAC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.71&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1rv6|1rv6]], [[2c7w|2c7w]], [[1qsv|1qsv]], [[2vwe|2vwe]], [[1qty|1qty]], [[1qsz|1qsz]], [[1flt|1flt]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=2xac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xac OCA], [https://pdbe.org/2xac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xac RCSB], [https://www.ebi.ac.uk/pdbsum/2xac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xac 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=2xac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xac OCA], [https://pdbe.org/2xac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xac RCSB], [https://www.ebi.ac.uk/pdbsum/2xac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xac ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages.  Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/VEGFB_HUMAN VEGFB_HUMAN]] Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis. [[https://www.uniprot.org/uniprot/VGFR1_HUMAN VGFR1_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.<ref>PMID:8248162</ref> <ref>PMID:18593464</ref> <ref>PMID:18515749</ref> <ref>PMID:20512933</ref> <ref>PMID:7824266</ref> <ref>PMID:8605350</ref> <ref>PMID:9299537</ref> <ref>PMID:11141500</ref> <ref>PMID:11811792</ref> <ref>PMID:11312102</ref> <ref>PMID:14633857</ref> <ref>PMID:12796773</ref> <ref>PMID:15735759</ref> <ref>PMID:16685275</ref> <ref>PMID:18079407</ref> <ref>PMID:18583712</ref> <ref>PMID:20551949</ref> <ref>PMID:21752276</ref> 
[https://www.uniprot.org/uniprot/VEGFB_HUMAN VEGFB_HUMAN] Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 40: Line 37:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Acharya KR]]
[[Category: Acharya, K R]]
[[Category: Darley P]]
[[Category: Darley, P]]
[[Category: Iyer S]]
[[Category: Iyer, S]]
[[Category: Angiogenesis]]
[[Category: Cysteine-knot protein]]
[[Category: Mitogen]]
[[Category: Signaling protein]]
[[Category: Transferase]]
[[Category: Transferase-signaling protein complex]]

Revision as of 13:27, 20 December 2023

Structural Insights into the Binding of VEGF-B by VEGFR-1D2: Recognition and SpecificityStructural Insights into the Binding of VEGF-B by VEGFR-1D2: Recognition and Specificity

Structural highlights

2xac is a 4 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 2.71Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VEGFB_HUMAN Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The formation of blood vessels (angiogenesis) is a highly orchestrated sequence of events involving crucial receptor-ligand interactions. Angiogenesis is critical for physiological processes such as development, wound healing, reproduction, tissue regeneration, and remodeling. It also plays a major role in sustaining tumor progression and chronic inflammation. Vascular endothelial growth factor (VEGF)-B, a member of the VEGF family of angiogenic growth factors, effects blood vessel formation by binding to a tyrosine kinase receptor, VEGFR-1. There is growing evidence of the important role played by VEGF-B in physiological and pathological vasculogenesis. Development of VEGF-B antagonists, which inhibit the interaction of this molecule with its cognate receptor, would be important for the treatment of pathologies associated specifically with this growth factor. In this study, we present the crystal structure of the complex of VEGF-B with domain 2 of VEGFR-1 at 2.7 A resolution. Our analysis reveals that each molecule of the ligand engages two receptor molecules using two symmetrical binding sites. Based on these interactions, we identify the receptor-binding determinants on VEGF-B and shed light on the differences in specificity towards VEGFR-1 among the different VEGF homologs.

Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity.,Iyer S, Darley PI, Acharya KR J Biol Chem. 2010 Jul 30;285(31):23779-89. Epub 2010 May 25. PMID:20501651[1]

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

See Also

References

  1. ↑ Iyer S, Darley PI, Acharya KR. Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity. J Biol Chem. 2010 Jul 30;285(31):23779-89. Epub 2010 May 25. PMID:20501651 doi:10.1074/jbc.M110.130658

2xac, resolution 2.71Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2xac&oldid=3994746"