2j8l

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(New page: 200px<br /> <applet load="2j8l" size="450" color="white" frame="true" align="right" spinBox="true" caption="2j8l" /> '''FXI APPLE 4 DOMAIN LOOP-OUT CONFORMATION'''...)
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[[Image:2j8l.gif|left|200px]]<br />
 
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<applet load="2j8l" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2j8l" />
 
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'''FXI APPLE 4 DOMAIN LOOP-OUT CONFORMATION'''<br />
 
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==Overview==
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==FXI Apple 4 domain loop-out conformation==
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Factor XI (FXI) is a homodimeric blood coagulation protein. Each monomer, comprises four tandem apple-domain repeats (A1-A4) and a serine protease, domain. We report here the NMR solution structure of the A4 domain, (residues 272-361), which mediates formation of the disulfide-linked FXI, dimer. A4 exhibits characteristic features of the plasminogen apple, nematode domain family, including a five-stranded beta-sheet flanked by an, alpha-helix on one side and a two-stranded beta-sheet on the other. In, addition, the solution structure reveals a second alpha-helix at the C, terminus. Comparison with a recent crystal structure of full-length FXI, combined with molecular modeling, suggests that the C-terminal helix is, formed only upon proteolytic activation. The newly formed helix disrupts, interdomain contacts and reorients the catalytic domains, bringing the, active sites into close proximity. This hypothesis is supported by, small-angle x-ray scattering and electron microscopy data, which indicate, that FXI activation is accompanied by a major change in shape. The results, are consistent with biochemical evidence that activated FXI cleaves its, substrate at two positions without release of an intermediate.
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<StructureSection load='2j8l' size='340' side='right'caption='[[2j8l]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2j8l]] is a 2 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=2J8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J8L FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 14 models</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2j8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j8l OCA], [https://pdbe.org/2j8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j8l RCSB], [https://www.ebi.ac.uk/pdbsum/2j8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j8l ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j8/2j8l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2j8l ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Factor XI (FXI) is a homodimeric blood coagulation protein. Each monomer comprises four tandem apple-domain repeats (A1-A4) and a serine protease domain. We report here the NMR solution structure of the A4 domain (residues 272-361), which mediates formation of the disulfide-linked FXI dimer. A4 exhibits characteristic features of the plasminogen apple nematode domain family, including a five-stranded beta-sheet flanked by an alpha-helix on one side and a two-stranded beta-sheet on the other. In addition, the solution structure reveals a second alpha-helix at the C terminus. Comparison with a recent crystal structure of full-length FXI, combined with molecular modeling, suggests that the C-terminal helix is formed only upon proteolytic activation. The newly formed helix disrupts interdomain contacts and reorients the catalytic domains, bringing the active sites into close proximity. This hypothesis is supported by small-angle x-ray scattering and electron microscopy data, which indicate that FXI activation is accompanied by a major change in shape. The results are consistent with biochemical evidence that activated FXI cleaves its substrate at two positions without release of an intermediate.
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==Disease==
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Solution structure of the A4 domain of factor XI sheds light on the mechanism of zymogen activation.,Samuel D, Cheng H, Riley PW, Canutescu AA, Nagaswami C, Weisel JW, Bu Z, Walsh PN, Roder H Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15693-8. Epub 2007 Sep 20. PMID:17884987<ref>PMID:17884987</ref>
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Known diseases associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]], Factor XI deficiency, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2J8L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J8L OCA].
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</div>
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<div class="pdbe-citations 2j8l" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Solution structure of the A4 domain of factor XI sheds light on the mechanism of zymogen activation., Samuel D, Cheng H, Riley PW, Canutescu AA, Nagaswami C, Weisel JW, Bu Z, Walsh PN, Roder H, Proc Natl Acad Sci U S A. 2007 Sep 20;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17884987 17884987]
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*[[Factor XIa 3D structures|Factor XIa 3D structures]]
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[[Category: Coagulation factor XIa]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bu, Z.]]
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[[Category: Bu Z]]
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[[Category: Canutescu, A.A.]]
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[[Category: Canutescu AA]]
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[[Category: Cheng, H.]]
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[[Category: Cheng H]]
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[[Category: N, P.]]
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[[Category: Riley PW]]
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[[Category: Riley, P.W.]]
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[[Category: Roder H]]
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[[Category: Roder, H.]]
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[[Category: Samuel D]]
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[[Category: Samuel, D.]]
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[[Category: Walsh PN]]
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[[Category: Walsh]]
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[[Category: alternative splicing]]
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[[Category: disease mutation]]
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[[Category: fxi / blood coagulation / pan domain /apple domain / blood coagulation]]
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[[Category: glycoprotein]]
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[[Category: heparin-binding]]
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[[Category: hydrolase]]
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[[Category: polymorphism]]
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[[Category: protease]]
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[[Category: serine protease]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:52:57 2007''
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Current revision

FXI Apple 4 domain loop-out conformation

PDB ID 2j8l

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