Fibrillin-1 misfolding and disease.
Fibrillin-1 is a 350 kDa calcium-binding protein which assembles to form 10-12 nm microfibrils in the extracellular matrix (ECM). The structure of fibrillin-1 is dominated by two types of disulfide-rich motifs, the calcium- binding epidermal growth factor-like (cbEGF) and transforming growth factor...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1797074856052785152 |
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| author | Whiteman, P Hutchinson, S Handford, P |
| author_facet | Whiteman, P Hutchinson, S Handford, P |
| author_sort | Whiteman, P |
| collection | OXFORD |
| description | Fibrillin-1 is a 350 kDa calcium-binding protein which assembles to form 10-12 nm microfibrils in the extracellular matrix (ECM). The structure of fibrillin-1 is dominated by two types of disulfide-rich motifs, the calcium- binding epidermal growth factor-like (cbEGF) and transforming growth factor beta binding protein-like (TB) domains. Disruption of fibrillin-1 domain structure and function contributes to the pathogenic mechanisms underlying two inherited diseases with very different etiologies: Marfan syndrome (MFS) and homocystinuria (HC). MFS is a connective tissue disease caused by mutations in the fibrillin-1 gene FBN1. Many missense mutations cause variable degrees of fibrillin-1 domain misfolding, which may affect the delivery of fibrillin-1 to the ECM and/or its assembly into microfibrils. HC is a metabolic disorder which affects methionine metabolism and results in raised serum levels of the highly reactive thiol-containing amino acid homocysteine. Patients with HC often exhibit ocular and skeletal defects resembling the MFS phenotype, suggesting that elevated homocysteine levels may lead to chemical reduction of disulfide bonds within fibrillin-1 domains resulting in the loss of native structure. Protein misfolding therefore is implicated in pathogenic mechanisms underlying MFS and HC. |
| first_indexed | 2024-03-06T23:42:16Z |
| format | Journal article |
| id | oxford-uuid:6fbbe3ca-0951-4c55-b8db-2c5c5c60a416 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:42:16Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:6fbbe3ca-0951-4c55-b8db-2c5c5c60a4162022-03-26T19:32:30ZFibrillin-1 misfolding and disease.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6fbbe3ca-0951-4c55-b8db-2c5c5c60a416EnglishSymplectic Elements at Oxford2006Whiteman, PHutchinson, SHandford, PFibrillin-1 is a 350 kDa calcium-binding protein which assembles to form 10-12 nm microfibrils in the extracellular matrix (ECM). The structure of fibrillin-1 is dominated by two types of disulfide-rich motifs, the calcium- binding epidermal growth factor-like (cbEGF) and transforming growth factor beta binding protein-like (TB) domains. Disruption of fibrillin-1 domain structure and function contributes to the pathogenic mechanisms underlying two inherited diseases with very different etiologies: Marfan syndrome (MFS) and homocystinuria (HC). MFS is a connective tissue disease caused by mutations in the fibrillin-1 gene FBN1. Many missense mutations cause variable degrees of fibrillin-1 domain misfolding, which may affect the delivery of fibrillin-1 to the ECM and/or its assembly into microfibrils. HC is a metabolic disorder which affects methionine metabolism and results in raised serum levels of the highly reactive thiol-containing amino acid homocysteine. Patients with HC often exhibit ocular and skeletal defects resembling the MFS phenotype, suggesting that elevated homocysteine levels may lead to chemical reduction of disulfide bonds within fibrillin-1 domains resulting in the loss of native structure. Protein misfolding therefore is implicated in pathogenic mechanisms underlying MFS and HC. |
| spellingShingle | Whiteman, P Hutchinson, S Handford, P Fibrillin-1 misfolding and disease. |
| title | Fibrillin-1 misfolding and disease. |
| title_full | Fibrillin-1 misfolding and disease. |
| title_fullStr | Fibrillin-1 misfolding and disease. |
| title_full_unstemmed | Fibrillin-1 misfolding and disease. |
| title_short | Fibrillin-1 misfolding and disease. |
| title_sort | fibrillin 1 misfolding and disease |
| work_keys_str_mv | AT whitemanp fibrillin1misfoldinganddisease AT hutchinsons fibrillin1misfoldinganddisease AT handfordp fibrillin1misfoldinganddisease |