Proteopedia

4je4: Difference between revisions

← Older edit
No edit summary
No edit summary
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4je4]] 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=4JE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JE4 FirstGlance]. <br>
</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [https://pdbe.org/4je4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [https://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></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]] 2.31&#8491;</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=4je4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je4 OCA], [https://pdbe.org/4je4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4je4 RCSB], [https://www.ebi.ac.uk/pdbsum/4je4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4je4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
Line 10: Line 11:
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  
[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dependent oncogenic transformation, but the precise signaling mechanisms of SHP2 are not well understood. We have developed binding proteins, termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular expression followed by interactome analysis showed that the monobodies are essentially monospecific to SHP2. Two crystal structures revealed that the monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the segments of both monobodies that bind to the peptide-binding grooves run in the opposite direction to that of canonical phosphotyrosine peptides, which may contribute to their exquisite specificity. When expressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was sufficient to inhibit two tyrosine phosphorylation events that are critical for SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N-SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phosphorylation of paxillin and signal transducer and activator of transcription 5. Our results delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent and specific antagonists of protein-protein interactions in cancer cells.
Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.,Sha F, Gencer EB, Georgeon S, Koide A, Yasui N, Koide S, Hantschel O Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14924-9. doi:, 10.1073/pnas.1303640110. Epub 2013 Aug 26. PMID:23980151<ref>PMID:23980151</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4je4" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

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

OCA
Retrieved from "https://proteopedia.openfox.io/w/4je4"