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2m8i

From Proteopedia

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Current revision

Structure of Pin1 WW domain

Structural highlights

2m8i is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PIN1_HUMAN Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Proteins and nucleic acids maintain the crowded interior of a living cell and can reach concentrations in the order of 200-400 g/L which affects the physicochemical parameters of the environment, such as viscosity and hydrodynamic as well as nonspecific strong repulsive and weak attractive interactions. Dynamics, structure, and activity of macromolecules were demonstrated to be affected by these parameters. However, it remains controversially debated, which of these factors are the dominant cause for the observed alterations in vivo. In this study we investigated the globular folded peptidyl-prolyl isomerase Pin1 in Xenopus laevis oocytes and in native-like crowded oocyte extract by in-cell NMR spectroscopy. We show that active Pin1 is driven into nonspecific weak attractive interactions with intracellular proteins prior to substrate recognition. The substrate recognition site of Pin1 performs specific and nonspecific attractive interactions. Phosphorylation of the WW domain at Ser16 by PKA abrogates both substrate recognition and the nonspecific interactions with the endogenous proteins. Our results validate the hypothesis formulated by McConkey that the majority of globular folded proteins with surface charge properties close to neutral under physiological conditions reside in macromolecular complexes with other sticky proteins due to molecular crowding. In addition, we demonstrate that commonly used synthetic crowding agents like Ficoll 70 are not suitable to mimic the intracellular environment due to their incapability to simulate biologically important weak attractive interactions.

Molecular crowding drives active Pin1 into nonspecific complexes with endogenous proteins prior to substrate recognition.,Luh LM, Hansel R, Lohr F, Kirchner DK, Krauskopf K, Pitzius S, Schafer B, Tufar P, Corbeski I, Guntert P, Dotsch V J Am Chem Soc. 2013 Sep 18;135(37):13796-803. doi: 10.1021/ja405244v. Epub 2013, Sep 6. PMID:23968199^[4]

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

References

↑ Dougherty MK, Muller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, Conrads TP, Veenstra TD, Lu KP, Morrison DK. Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell. 2005 Jan 21;17(2):215-24. PMID:15664191 doi:10.1016/j.molcel.2004.11.055
↑ Yu L, Mohamed AJ, Vargas L, Berglof A, Finn G, Lu KP, Smith CI. Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1. J Biol Chem. 2006 Jun 30;281(26):18201-7. Epub 2006 Apr 27. PMID:16644721 doi:10.1074/jbc.M603090200
↑ Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, Zhang YJ, Goate A, Chen RH, Zhou XZ, Lu KP. Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol Cell. 2011 Apr 22;42(2):147-59. doi: 10.1016/j.molcel.2011.03.005. Epub 2011 , Apr 14. PMID:21497122 doi:10.1016/j.molcel.2011.03.005
↑ Luh LM, Hansel R, Lohr F, Kirchner DK, Krauskopf K, Pitzius S, Schafer B, Tufar P, Corbeski I, Guntert P, Dotsch V. Molecular crowding drives active Pin1 into nonspecific complexes with endogenous proteins prior to substrate recognition. J Am Chem Soc. 2013 Sep 18;135(37):13796-803. doi: 10.1021/ja405244v. Epub 2013, Sep 6. PMID:23968199 doi:http://dx.doi.org/10.1021/ja405244v

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/2m8i"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2m8i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M8I 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=2m8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8i OCA], [https://pdbe.org/2m8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m8i RCSB], [https://www.ebi.ac.uk/pdbsum/2m8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8i ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2m8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8i OCA], [https://pdbe.org/2m8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m8i RCSB], [https://www.ebi.ac.uk/pdbsum/2m8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8i ProSAT]</span></td></tr>
 </table>
 == Function ==

2m8i

From Proteopedia

Current revision

Structure of Pin1 WW domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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