2w86 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.
FBN1_HUMAN Defects in FBN1 are a cause of Marfan syndrome (MFS) [MIM: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.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Defects in FBN1 are a cause of ectopia lentis, isolated, autosomal dominant (ECTOL1) [MIM:129600. An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation.[34][35][36][37] Defects in FBN1 are the cause of Weill-Marchesani syndrome 2 (WMS2) [MIM:608328. A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma.[38] Defects in FBN1 are a cause of Shprintzen-Goldberg craniosynostosis syndrome (SGS) [MIM: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: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.[39] Defects in FBN1 are a cause of stiff skin syndrome (SSKS) [MIM: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.[40] Defects in FBN1 are the cause of geleophysic dysplasia type 2 (GPHYSD2) [MIM: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.[41] Defects in FBN1 are the cause of acromicric dysplasia (ACMICD) [MIM: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.[42]
Function
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).[43]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[44]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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↑Le Goff C, Mahaut C, Wang LW, Allali S, Abhyankar A, Jensen S, Zylberberg L, Collod-Beroud G, Bonnet D, Alanay Y, Brady AF, Cordier MP, Devriendt K, Genevieve D, Kiper PO, Kitoh H, Krakow D, Lynch SA, Le Merrer M, Megarbane A, Mortier G, Odent S, Polak M, Rohrbach M, Sillence D, Stolte-Dijkstra I, Superti-Furga A, Rimoin DL, Topouchian V, Unger S, Zabel B, Bole-Feysot C, Nitschke P, Handford P, Casanova JL, Boileau C, Apte SS, Munnich A, Cormier-Daire V. Mutations in the TGFbeta binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet. 2011 Jul 15;89(1):7-14. doi: 10.1016/j.ajhg.2011.05.012. Epub, 2011 Jun 16. PMID:21683322 doi:10.1016/j.ajhg.2011.05.012
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↑Jensen SA, Iqbal S, Lowe ED, Redfield C, Handford PA. Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins. Structure. 2009 May 13;17(5):759-68. PMID:19446531 doi:10.1016/j.str.2009.03.014
