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3zu7

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Revision as of 03:15, 5 August 2016

Crystal structure of a designed selected Ankyrin Repeat protein in complex with the MAP kinase ERK2

Structural highlights

3zu7 is a 2 chain structure with sequence from Buffalo rat and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3erk, 2gph, 1gol, 4erk, 1erk, 2erk, 3zuv
Activity:	Mitogen-activated protein kinase, with EC number 2.7.11.24
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MK01_RAT] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.^[1] Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity (By similarity).^[2]

Publication Abstract from PubMed

We have selected designed ankyrin repeat proteins (DARPins) from a synthetic library by using ribosome display that selectively bind to the mitogen-activated protein kinase ERK2 (extracellular signal-regulated kinase 2) in either its nonphosphorylated (inactive) or doubly phosphorylated (active) form. They do not bind to other kinases tested. Crystal structures of complexes with two DARPins, each specific for one of the kinase forms, were obtained. The two DARPins bind to essentially the same region of the kinase, but recognize the conformational change within the activation loop and an adjacent area, which is the key structural difference that occurs upon activation. Whereas the rigid phosphorylated activation loop remains in the same form when bound by the DARPin, the more mobile unphosphorylated loop is pushed to a new position. The DARPins can be used to selectively precipitate the cognate form of the kinases from cell lysates. They can also specifically recognize the modification status of the kinase inside the cell. By fusing the kinase with Renilla luciferase and the DARPin to GFP, an energy transfer from luciferase to GFP can be observed in COS-7 cells upon intracellular complex formation. Phosphorylated ERK2 is seen to increase by incubation of the COS-7 cells with FBS and to decrease upon adding the ERK pathway inhibitor PD98509. Furthermore, the anti-ERK2 DARPin is seen to inhibit ERK phosphorylation as it blocks the target inside the cell. This strategy of creating activation-state-specific sensors and kinase-specific inhibitors may add to the repertoire to investigate intracellular signaling in real time.

Structural and functional analysis of phosphorylation-specific binders of the kinase ERK from designed ankyrin repeat protein libraries.,Kummer L, Parizek P, Rube P, Millgramm B, Prinz A, Mittl PR, Kaufholz M, Zimmermann B, Herberg FW, Pluckthun A Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):E2248-57. Epub 2012 Jul 27. PMID:22843676^[3]

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

References

↑ Ma W, Shang Y, Wei Z, Wen W, Wang W, Zhang M. Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase. Structure. 2010 Nov 10;18(11):1502-11. PMID:21070949 doi:10.1016/j.str.2010.08.011
↑ Ma W, Shang Y, Wei Z, Wen W, Wang W, Zhang M. Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase. Structure. 2010 Nov 10;18(11):1502-11. PMID:21070949 doi:10.1016/j.str.2010.08.011
↑ Kummer L, Parizek P, Rube P, Millgramm B, Prinz A, Mittl PR, Kaufholz M, Zimmermann B, Herberg FW, Pluckthun A. Structural and functional analysis of phosphorylation-specific binders of the kinase ERK from designed ankyrin repeat protein libraries. Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):E2248-57. Epub 2012 Jul 27. PMID:22843676 doi:http://dx.doi.org/10.1073/pnas.1205399109

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/3zu7"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a designed selected Ankyrin Repeat protein in complex with the MAP kinase ERK2==
 <StructureSection load='3zu7' size='340' side='right' caption='[[3zu7]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zu7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZU7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZU7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zu7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZU7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZU7 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3erk|3erk]], [[2gph|2gph]], [[1gol|1gol]], [[4erk|4erk]], [[1erk|1erk]], [[2erk|2erk]], [[3zuv|3zuv]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3zu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zu7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zu7 RCSB], [http://www.ebi.ac.uk/pdbsum/3zu7 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=3zu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zu7 OCA], [http://pdbe.org/3zu7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zu7 RCSB], [http://www.ebi.ac.uk/pdbsum/3zu7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zu7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3zu7" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Mitogen-activated protein kinase]]
-[[Category: Rattus norvegicus]]
+[[Category: Synthetic construct sequences]]
-[[Category: Synthetic construct]]
 [[Category: Kummer, L]]
 [[Category: Mittl, P R]]

3zu7

From Proteopedia

Revision as of 03:15, 5 August 2016

Crystal structure of a designed selected Ankyrin Repeat protein in complex with the MAP kinase ERK2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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