Fibrillin

Fibrillin-2 has an amino acid sequence that is 68% identical to fibrillin-1 and is coexpressed with fibrillin-1 in many tissues early in mammalian development. It forms head-to-tail fibrillinl/2 alternating heterodimers that resemble fibrillin-1 homodimers shown at the top of Fig. 6.3. During mammalian development, some tissues express fibrillin-2 without fibrillin-1 and fibrillin-2 homodimers may assemble by a mechanism that does not involve fibrillin-1 but perhaps utilizing fibrillin-3, a third member of the fibrillin family. Fibrillin-2 binds to the precursor of elastin during development and forms stronger elastic fibers than fibrillin-1. Fibrillin-3 is a minor component whose functions are uncertain. 

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EGF-like domains were identified in extracellular proteins such as fibrillin-1. EGF-modules contain about 40-45 amino acids including six cysteine residues which normally build S-S disulfide bond bridges. Mutations in the fibrillin-1 gene cause Marfan syndrome and related disorders. 

MARFAN SYNDROME IS DUE TO MUTATIONS IN THE GENE FOR FIBRILLIN, A PROTEIN PRESENT IN MICROFIBRILS... 

Edgar There is more DNA per unit area, there is more green fluorescent protein per unit area. In endoreplicating cells we have looked for one nucleolar protein, fibrillin, which is massively overexpressed in Myc-overexpressing cells. 

EGF-domains External growth factor but general protein assembly control e.g. fibrillin... 

Type XVI collagen is composed of 10 collagenous domains (COLI-COLIO) flanked by 11 NC domains. Type XVI collagen localizes near the dermal-epidermal junction. From immunoelectron microscopy of the papillary dermis, type XVI collagen associates with a fibrillin-1-containing matrix but not on collagen fibrils. ... 

Molecular analysis of the fibrillin gene in these family members identified the mutation associated with Marfan syndrome as a single base substitution at the 3 end of exon 2. The result of this substitution was a deletion of the entire exon 2 firom the mRNA, and consequently 41 amino acids from the fibrillin protein. The mutation was most likely a... 

Answer A. Homocysteine, the substrate for the enzyme, accumulates increasing the risk of deep vein thrombosis and disrupting the normal crosslinking of fibrillin. Deficiency of homocysteine methyl transferase would cause homocystinuria, but would also predispose to megaloblastic anemia. 

Fibrillin, calcium binding, 46 473, 474, 477 Fibulin-I, calcium binding, 46 473 Field desorption mass spectroscopy, 28 6, 21 Field effects, of astatophenols, 31 66 Fine structure, 13 193-204 Fingerprinting of polymetalates, 19 246-248 Finite perturbation theory, 22 211, 212 First transition series, substitution, transferrins, 41 423 26... 

Dominant negative effect, when the mutant protein interferes with function of the normal protein Osteogenesis imperfecta and the collagen 1A gene (COLIAI) Marfan syndrome and the fibrillin-1 gene (FBNI)... 

Many tissues, such as lung, blood vessels, and skin, require elasticity for proper function this property is fulfilled by the matrix elastic fibers, which are composed of the proteins elastin and fibrillin. 

Marfan syndrome arises from a mutation in the gene encoding fibrillin- 7IFBN... 

The pattern of inheritance of Marfan syndrome is autosomal dominant due to the failure of elastic fibers to assemble properly upon interaction of mutant fibrillin with normal elastin. 

Function and location of elastin Cause of Marfan syn drome Elastin is a connective tissue protein with rubber-like properties. Elastic fibers composed of elastin and glycoprotein microfibrils, such as fibrillin, are found in the lungs, the walls of large arteries, and elastic ligaments. [Note Mutations in the fibrillin gene are responsible for Marfan syndrome]... 

In addition, the tetramers are seen to interact to form long chains (beaded filaments). Dimers, tetramers, and polymeric chains all have 30-75-30 nm spacing between the globular ends (Furthmayr et al., 1983 Von Der Mark et al., 1984 Wu et al., 1987). Collagen VI is found to bind to hyaluronan (Kielty et al., 1992), biglycan and decorin (Wiberg et al., 2001), fibrillin (Ueda and Yue, 2003), and other matrix constituents. 

C. Fibrillin-1 Interactions with Microfibril-Associated Molecules. 414... 

Fibrillin microfibrils are widely distributed extracellular matrix assemblies that endow elastic and non elastic connective tissues with long-range elasticity. They direct tropoelastin deposition during elastic fibrillogenesis and form an outer mantle for mature elastic fibers. Microfibril arrays are also abundant in dynamic tissues that do not express elastin, such as the ciliary zonules of the eye. Mutations in fibrillin-1—the principal structural component of microfibrils—cause Marfan syndrome, a heritable disease with severe aortic, ocular, and skeletal defects. Isolated fibrillin-rich microfibrils have a complex 56 nm beads-on-a-string appearance the molecular basis of their assembly and... 

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