View source for 2w86


==Crystal structure of fibrillin-1 domains cbEGF9hyb2cbEGF10, calcium saturated form==
<StructureSection load='2w86' size='340' side='right'caption='[[2w86]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2w86]] 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=2W86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W86 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=2w86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w86 OCA], [https://pdbe.org/2w86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w86 RCSB], [https://www.ebi.ac.uk/pdbsum/2w86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w86 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FBN1_HUMAN FBN1_HUMAN] Defects in FBN1 are a cause of Marfan syndrome (MFS) [MIM:[https://omim.org/entry/154700 154700]. MFS is an autosomal dominant disorder that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with MFS, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in up to about 80% of MFS patients and is almost always bilateral. The leading cause of premature death in MFS patients is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. Note=The majority of the more than 600 mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.<ref>PMID:15221638</ref> <ref>PMID:1852208</ref> <ref>PMID:1301946</ref> <ref>PMID:1569206</ref> <ref>PMID:8406497</ref> <ref>PMID:8504310</ref> <ref>PMID:8281141</ref> <ref>PMID:7977366</ref> <ref>PMID:8004112</ref> <ref>PMID:8040326</ref> <ref>PMID:8071963</ref> <ref>PMID:7870075</ref> <ref>PMID:8136837</ref> <ref>PMID:7611299</ref> <ref>PMID:7738200</ref> <ref>PMID:8882780</ref> <ref>PMID:8863159</ref> <ref>PMID:9254848</ref> <ref>PMID:9338581</ref> <ref>PMID:9837823</ref> <ref>PMID:9452085</ref> <ref>PMID:10694921</ref> <ref>PMID:10441597</ref> <ref>PMID:10425041</ref> <ref>PMID:11700157</ref> <ref>PMID:12203992</ref> <ref>PMID:11826022</ref> <ref>PMID:14695540</ref> <ref>PMID:15161917</ref> <ref>PMID:16222657</ref> <ref>PMID:16220557</ref> <ref>PMID:20803651</ref> <ref>PMID:21542060</ref>   Defects in FBN1 are a cause of ectopia lentis, isolated, autosomal dominant (ECTOL1) [MIM:[https://omim.org/entry/129600 129600]. An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation.<ref>PMID:11700157</ref> <ref>PMID:12203992</ref> <ref>PMID:11826022</ref> <ref>PMID:8188302</ref>   Defects in FBN1 are the cause of Weill-Marchesani syndrome 2 (WMS2) [MIM:[https://omim.org/entry/608328 608328]. A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma.<ref>PMID:12525539</ref>   Defects in FBN1 are a cause of Shprintzen-Goldberg craniosynostosis syndrome (SGS) [MIM:[https://omim.org/entry/182212 182212]. SGS is a very rare syndrome characterized by a marfanoid habitus, craniosynostosis, characteristic dysmorphic facial features, skeletal and cardiovascular abnormalities, mental retardation, developmental delay and learning disabilities.[:]  Defects in FBN1 are a cause of overlap connective tissue disease (OCTD) [MIM:[https://omim.org/entry/604308 604308]. A heritable disorder of connective tissue characterized by involvement of the mitral valve, aorta, skeleton, and skin. MASS syndrome is closely resembling both the Marfan syndrome and the Barlow syndrome. However, no dislocation of the lenses or aneurysmal changes occur in the aorta, and the mitral valve prolapse is by no means invariable.<ref>PMID:2739055</ref>   Defects in FBN1 are a cause of stiff skin syndrome (SSKS) [MIM:[https://omim.org/entry/184900 184900]. It is a syndrome characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness.<ref>PMID:20375004</ref>   Defects in FBN1 are the cause of geleophysic dysplasia type 2 (GPHYSD2) [MIM:[https://omim.org/entry/614185 614185]. An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues.<ref>PMID:21683322</ref>   Defects in FBN1 are the cause of acromicric dysplasia (ACMICD) [MIM:[https://omim.org/entry/102370 102370]. An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have distinct facial features, including round face, well-defined eyebrows, long eyelashes, bulbous nose with anteverted nostrils, long and prominent philtrum, and thick lips with a small mouth. Other characteristic features include hoarse voice and pseudomuscular build, and there are distinct skeletal features as well, including an internal notch of the femoral head, internal notch of the second metacarpal, and external notch of the fifth metacarpal.<ref>PMID:21683322</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FBN1_HUMAN FBN1_HUMAN] Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. Fibrillin-1-containing microfibrils provide long-term force bearing structural support. Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (By similarity).<ref>PMID:15062093</ref> 
== 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/w8/2w86_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2w86 ConSurf].
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== Publication Abstract from PubMed ==
The fibrillins and latent transforming growth factor-beta binding proteins (LTBPs) form a superfamily of structurally-related proteins consisting of calcium-binding epidermal growth factor-like (cbEGF) domains interspersed with 8-cysteine-containing transforming growth factor beta-binding protein-like (TB) and hybrid (hyb) domains. Fibrillins are the major components of the extracellular 10-12 nm diameter microfibrils, which mediate a variety of cell-matrix interactions. Here we present the crystal structure of a fibrillin-1 cbEGF9-hyb2-cbEGF10 fragment, solved to 1.8 A resolution. The hybrid domain fold is similar, but not identical, to the TB domain fold seen in previous fibrillin-1 and LTBP-1 fragments. Pairwise interactions with neighboring cbEGF domains demonstrate extensive interfaces, with the hyb2-cbEGF10 interface dependent on Ca(2+) binding. These observations provide accurate constraints for models of fibrillin organization within the 10-12 nm microfibrils and provide further molecular insights into how Ca(2+) binding influences the intermolecular interactions and biomechanical properties of fibrillin-1.

Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins.,Jensen SA, Iqbal S, Lowe ED, Redfield C, Handford PA Structure. 2009 May 13;17(5):759-68. PMID:19446531<ref>PMID:19446531</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2w86" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Handford PA]]
[[Category: Iqbal S]]
[[Category: Jensen SA]]
[[Category: Lowe ED]]
[[Category: Redfield C]]