7nzc

From Proteopedia

(Difference between revisions)

Current revision

First SH3 domain of POSH (Plenty of SH3 Domains protein)

Structural highlights

7nzc is a 1 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 1.111Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SH3R1_HUMAN Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity).[UniProtKB:Q69ZI1]^[1] ^[2] ^[3] (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity.^[4]

Publication Abstract from PubMed

Aromatic residues cluster in the core of folded proteins, where they stabilize the structure through multiple interactions. Nuclear magnetic resonance (NMR) studies in the 1970s showed that aromatic side chains can undergo ring flips-that is, 180 degrees rotations-despite their role in maintaining the protein fold(1-3). It was suggested that large-scale 'breathing' motions of the surrounding protein environment would be necessary to accommodate these ring flipping events(1). However, the structural details of these motions have remained unclear. Here we uncover the structural rearrangements that accompany ring flipping of a buried tyrosine residue in an SH3 domain. Using NMR, we show that the tyrosine side chain flips to a low-populated, minor state and, through a proteome-wide sequence analysis, we design mutants that stabilize this state, which allows us to capture its high-resolution structure by X-ray crystallography. A void volume is generated around the tyrosine ring during the structural transition between the major and minor state, and this allows fast flipping to take place. Our results provide structural insights into the protein breathing motions that are associated with ring flipping. More generally, our study has implications for protein design and structure prediction by showing how the local protein environment influences amino acid side chain conformations and vice versa.

Visualizing protein breathing motions associated with aromatic ring flipping.,Marino Perez L, Ielasi FS, Bessa LM, Maurin D, Kragelj J, Blackledge M, Salvi N, Bouvignies G, Palencia A, Jensen MR Nature. 2022 Feb;602(7898):695-700. doi: 10.1038/s41586-022-04417-6. Epub 2022, Feb 16. PMID:35173330^[5]

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

References

↑ Alroy I, Tuvia S, Greener T, Gordon D, Barr HM, Taglicht D, Mandil-Levin R, Ben-Avraham D, Konforty D, Nir A, Levius O, Bicoviski V, Dori M, Cohen S, Yaar L, Erez O, Propheta-Meiran O, Koskas M, Caspi-Bachar E, Alchanati I, Sela-Brown A, Moskowitz H, Tessmer U, Schubert U, Reiss Y. The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1478-83. Epub 2005 Jan 19. PMID:15659549 doi:http://dx.doi.org/0408717102
↑ Lin DH, Yue P, Pan CY, Sun P, Zhang X, Han Z, Roos M, Caplan M, Giebisch G, Wang WH. POSH stimulates the ubiquitination and the clathrin-independent endocytosis of ROMK1 channels. J Biol Chem. 2009 Oct 23;284(43):29614-24. doi: 10.1074/jbc.M109.041582. Epub, 2009 Aug 26. PMID:19710010 doi:http://dx.doi.org/10.1074/jbc.M109.041582
↑ Karkkainen S, van der Linden M, Renkema GH. POSH2 is a RING finger E3 ligase with Rac1 binding activity through a partial CRIB domain. FEBS Lett. 2010 Sep 24;584(18):3867-72. doi: 10.1016/j.febslet.2010.07.060. Epub , 2010 Aug 8. PMID:20696164 doi:http://dx.doi.org/10.1016/j.febslet.2010.07.060
↑ Alroy I, Tuvia S, Greener T, Gordon D, Barr HM, Taglicht D, Mandil-Levin R, Ben-Avraham D, Konforty D, Nir A, Levius O, Bicoviski V, Dori M, Cohen S, Yaar L, Erez O, Propheta-Meiran O, Koskas M, Caspi-Bachar E, Alchanati I, Sela-Brown A, Moskowitz H, Tessmer U, Schubert U, Reiss Y. The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1478-83. Epub 2005 Jan 19. PMID:15659549 doi:http://dx.doi.org/0408717102
↑ Marino Perez L, Ielasi FS, Bessa LM, Maurin D, Kragelj J, Blackledge M, Salvi N, Bouvignies G, Palencia A, Jensen MR. Visualizing protein breathing motions associated with aromatic ring flipping. Nature. 2022 Feb;602(7898):695-700. doi: 10.1038/s41586-022-04417-6. Epub 2022, Feb 16. PMID:35173330 doi:http://dx.doi.org/10.1038/s41586-022-04417-6

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/7nzc"

Categories: Homo sapiens | Large Structures | Bessa LM | Jensen MR | Palencia A

@@ Line 3: / Line 3: @@
 <StructureSection load='7nzc' size='340' side='right'caption='[[7nzc]], [[Resolution|resolution]] 1.11&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7nzc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NZC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7nzc]] is a 1 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=7NZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NZC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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]] 1.111&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></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=7nzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nzc OCA], [https://pdbe.org/7nzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nzc RCSB], [https://www.ebi.ac.uk/pdbsum/7nzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nzc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/SH3R1_HUMAN SH3R1_HUMAN]] Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity).[UniProtKB:Q69ZI1]<ref>PMID:15659549</ref> <ref>PMID:19710010</ref> <ref>PMID:20696164</ref>   (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity.<ref>PMID:15659549</ref>
+[https://www.uniprot.org/uniprot/SH3R1_HUMAN SH3R1_HUMAN] Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity).[UniProtKB:Q69ZI1]<ref>PMID:15659549</ref> <ref>PMID:19710010</ref> <ref>PMID:20696164</ref>   (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity.<ref>PMID:15659549</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 7nzc" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: RING-type E3 ubiquitin transferase]]
+[[Category: Bessa LM]]
-[[Category: Bessa, L M]]
+[[Category: Jensen MR]]
-[[Category: Jensen, M R]]
+[[Category: Palencia A]]
-[[Category: Palencia, A]]
-[[Category: Map-kinase scaffold activity ubiquitin protein ligase activity]]
-[[Category: Signaling protein]]

7nzc

From Proteopedia

Current revision

First SH3 domain of POSH (Plenty of SH3 Domains protein)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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