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- | [[Image:2qar.jpg|left|200px]] | |
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- | {{Structure
| + | ==Structure of the 2TEL crystallization module fused to T4 lysozyme with a helical linker.== |
- | |PDB= 2qar |SIZE=350|CAPTION= <scene name='initialview01'>2qar</scene>, resolution 2.400Å
| + | <StructureSection load='2qar' size='340' side='right'caption='[[2qar]], [[Resolution|resolution]] 2.40Å' scene=''> |
- | |SITE= <scene name='pdbsite=AC1:No3+Binding+Site+For+Residue+D+101'>AC1</scene>, <scene name='pdbsite=AC2:No3+Binding+Site+For+Residue+A+102'>AC2</scene>, <scene name='pdbsite=AC3:No3+Binding+Site+For+Residue+E+108'>AC3</scene>, <scene name='pdbsite=AC4:No3+Binding+Site+For+Residue+D+104'>AC4</scene>, <scene name='pdbsite=AC5:No3+Binding+Site+For+Residue+D+106'>AC5</scene>, <scene name='pdbsite=AC6:No3+Binding+Site+For+Residue+E+109'>AC6</scene>, <scene name='pdbsite=AC7:No3+Binding+Site+For+Residue+D+108'>AC7</scene>, <scene name='pdbsite=AC8:No3+Binding+Site+For+Residue+B+109'>AC8</scene>, <scene name='pdbsite=AC9:Nh4+Binding+Site+For+Residue+A+201'>AC9</scene> and <scene name='pdbsite=BC1:Nh4+Binding+Site+For+Residue+D+202'>BC1</scene>
| + | == Structural highlights == |
- | |LIGAND= <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>
| + | <table><tr><td colspan='2'>[[2qar]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QAR FirstGlance]. <br> |
- | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
- | |GENE= E ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10665 Enterobacteria phage T4])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> |
- | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qar OCA], [https://pdbe.org/2qar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qar RCSB], [https://www.ebi.ac.uk/pdbsum/2qar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qar ProSAT]</span></td></tr> |
- | |RELATEDENTRY=[[2qb0|2qb0]], [[2qb1|2QB1]]
| + | </table> |
- | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qar OCA], [http://www.ebi.ac.uk/pdbsum/2qar PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qar RCSB]</span>
| + | == Disease == |
- | }}
| + | [https://www.uniprot.org/uniprot/ETV6_HUMAN ETV6_HUMAN] Note=A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).<ref>PMID:12203785</ref> Note=Chromosomal aberrations involving ETV6 are found in a form of acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1; translocation t(4;12)(q12;p13) with CHIC2.<ref>PMID:7761424</ref> <ref>PMID:7780150</ref> <ref>PMID:15806161</ref> Note=Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1. Note=A chromosomal aberration involving ETV6 is found in a form of pre-B acute myeloid leukemia. Translocation t(9;12)(p24;p13) with JAK2. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2. Defects in ETV6 are a cause of myeloproliferative disorder chronic with eosinophilia (MPE) [MIM:[https://omim.org/entry/131440 131440]. A hematologic disorder characterized by malignant eosinophils proliferation. Note=A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein. Defects in ETV6 are a cause of acute myelogenous leukemia (AML) [MIM:[https://omim.org/entry/601626 601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.<ref>PMID:7761424</ref> <ref>PMID:7780150</ref> <ref>PMID:15806161</ref> Note=A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5. |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/ETV6_HUMAN ETV6_HUMAN] Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qa/2qar_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qar ConSurf]. |
| + | <div style="clear:both"></div> |
| | | |
- | '''Structure of the 2TEL crystallization module fused to T4 lysozyme with a helical linker.'''
| + | ==See Also== |
- | | + | *[[Lysozyme 3D structures|Lysozyme 3D structures]] |
- | | + | == References == |
- | ==Overview== | + | <references/> |
- | Obtaining well-diffracting crystals of macromolecules remains a significant barrier to structure determination. Here we propose and test a new approach to crystallization, in which the crystallization target is fused to a polymerizing protein module, so that polymer formation drives crystallization of the target. We test the approach using a polymerization module called 2TEL, which consists of two tandem sterile alpha motif (SAM) domains from the protein translocation Ets leukemia (TEL). The 2TEL module is engineered to polymerize as the pH is lowered, which allows the subtle modulation of polymerization needed for crystal formation. We show that the 2TEL module can drive the crystallization of 11 soluble proteins, including three that resisted prior crystallization attempts. In addition, the 2TEL module crystallizes in the presence of various detergents, suggesting that it might facilitate membrane protein crystallization. The crystal structures of two fusion proteins show that the TELSAM polymer is responsible for the majority of contacts in the crystal lattice. The results suggest that biological polymers could be designed as crystallization modules.
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure==
| + | |
- | 2QAR is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Enterobacteria_phage_t4 Enterobacteria phage t4] and [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QAR OCA].
| + | |
- | | + | |
- | ==Reference== | + | |
- | Polymer-driven crystallization., Nauli S, Farr S, Lee YJ, Kim HY, Faham S, Bowie JU, Protein Sci. 2007 Nov;16(11):2542-51. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17962407 17962407]
| + | |
- | [[Category: Enterobacteria phage t4]]
| + | |
| [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
- | [[Category: Lysozyme]] | + | [[Category: Escherichia virus T4]] |
- | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
- | [[Category: Bowie, J U.]] | + | [[Category: Bowie JU]] |
- | [[Category: Nauli, S.]] | + | [[Category: Nauli S]] |
- | [[Category: crystallization module]]
| + | |
- | [[Category: hydrolase regulator]]
| + | |
- | [[Category: polymer]]
| + | |
- | [[Category: sterile alpha motif]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:47:02 2008''
| + | |
| Structural highlights
Disease
ETV6_HUMAN Note=A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).[1] Note=Chromosomal aberrations involving ETV6 are found in a form of acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1; translocation t(4;12)(q12;p13) with CHIC2.[2] [3] [4] Note=Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1. Note=A chromosomal aberration involving ETV6 is found in a form of pre-B acute myeloid leukemia. Translocation t(9;12)(p24;p13) with JAK2. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2. Defects in ETV6 are a cause of myeloproliferative disorder chronic with eosinophilia (MPE) [MIM:131440. A hematologic disorder characterized by malignant eosinophils proliferation. Note=A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein. Defects in ETV6 are a cause of acute myelogenous leukemia (AML) [MIM:601626. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.[5] [6] [7] Note=A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5.
Function
ETV6_HUMAN Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Odero MD, Vizmanos JL, Roman JP, Lahortiga I, Panizo C, Calasanz MJ, Zeleznik-Le NJ, Rowley JD, Novo FJ. A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome. Genes Chromosomes Cancer. 2002 Sep;35(1):11-9. PMID:12203785 doi:10.1002/gcc.10090
- ↑ Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4917-21. PMID:7761424
- ↑ Romana SP, Mauchauffe M, Le Coniat M, Chumakov I, Le Paslier D, Berger R, Bernard OA. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood. 1995 Jun 15;85(12):3662-70. PMID:7780150
- ↑ Barjesteh van Waalwijk van Doorn-Khosrovani S, Spensberger D, de Knegt Y, Tang M, Lowenberg B, Delwel R. Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia. Oncogene. 2005 Jun 9;24(25):4129-37. PMID:15806161 doi:10.1038/sj.onc.1208588
- ↑ Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4917-21. PMID:7761424
- ↑ Romana SP, Mauchauffe M, Le Coniat M, Chumakov I, Le Paslier D, Berger R, Bernard OA. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood. 1995 Jun 15;85(12):3662-70. PMID:7780150
- ↑ Barjesteh van Waalwijk van Doorn-Khosrovani S, Spensberger D, de Knegt Y, Tang M, Lowenberg B, Delwel R. Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia. Oncogene. 2005 Jun 9;24(25):4129-37. PMID:15806161 doi:10.1038/sj.onc.1208588
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