1q2h

From Proteopedia

(Difference between revisions)

Revision as of 07:41, 9 December 2020

Phenylalanine Zipper Mediates APS Dimerization

Structural highlights

1q2h is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	APS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SH2B2_HUMAN] Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3.^[1] ^[2] ^[3] ^[4]

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 APS, SH2-B and LNK proteins are adapters that activate and modulate receptor tyrosine kinase and JAK/STAT signaling. We now show that a conserved N-terminal domain mediates APS homodimerization. We determined the crystal structure of the dimerization domain at a resolution of 1.7 A using bromide ion MAD phasing. Each molecule contributes two helices to a compact four-helix bundle having a bisecting-U topology. Its most conspicuous feature is a stack of interdigitated phenylalanine side chains at the domain core. These residues create a new motif we refer to as a 'phenylalanine zipper,' which is critical to dimerization. A newly developed bridging yeast tri-hybrid assay showed that APS dimerizes JAK2, insulin receptor and IGF1 receptor kinases using its SH2 and dimerization domains. Dimerization via the phenylalanine zipper domain provides a mechanism for activating and modulating tyrosine kinase activity even in the absence of extracellular ligands.

A phenylalanine zipper mediates APS dimerization.,Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE Nat Struct Mol Biol. 2004 Oct;11(10):968-74. Epub 2004 Sep 19. PMID:15378031^[5]

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

References

↑ Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A. APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl. Leukemia. 1999 May;13(5):760-7. PMID:10374881
↑ Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A. APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis. Oncogene. 1999 Jan 21;18(3):759-67. PMID:9989826 doi:http://dx.doi.org/10.1038/sj.onc.1202326
↑ Yabana N, Shibuya M. Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity. Oncogene. 2002 Oct 31;21(50):7720-9. PMID:12400014 doi:http://dx.doi.org/10.1038/sj.onc.1205927
↑ Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE. A phenylalanine zipper mediates APS dimerization. Nat Struct Mol Biol. 2004 Oct;11(10):968-74. Epub 2004 Sep 19. PMID:15378031 doi:10.1038/nsmb829
↑ Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI, Shoelson SE. A phenylalanine zipper mediates APS dimerization. Nat Struct Mol Biol. 2004 Oct;11(10):968-74. Epub 2004 Sep 19. PMID:15378031 doi:10.1038/nsmb829

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1q2h"

@@ Line 1: / Line 1: @@
 ==Phenylalanine Zipper Mediates APS Dimerization==
-<StructureSection load='1q2h' size='340' side='right' caption='[[1q2h]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='1q2h' size='340' side='right'caption='[[1q2h]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1q2h]] is a 3 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=1Q2H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Q2H FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1q2h]] is a 3 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=1Q2H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Q2H FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1q2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2h OCA], [http://pdbe.org/1q2h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q2h RCSB], [http://www.ebi.ac.uk/pdbsum/1q2h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q2h ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1q2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2h OCA], [http://pdbe.org/1q2h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q2h RCSB], [http://www.ebi.ac.uk/pdbsum/1q2h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q2h ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chi, Y I]]
 [[Category: Dhe-Paganon, S]]

1q2h

From Proteopedia

Revision as of 07:41, 9 December 2020

Phenylalanine Zipper Mediates APS Dimerization

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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