Biochemistry · Protein
Fibrillin-1 !
Fibrillin-1 forms microfibrils that support elastic fibres and store TGF-β; its variants cause Marfan syndrome.
Updated 2026-11-01
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Key facts
- Large glycoprotein (≈ 2,870 amino acids, FBN1 gene on chromosome 15) made mostly of calcium-binding EGF-like domains (cbEGF).
- Forms ≈ 10 nm microfibrils: the scaffold for elastin and the main component of the zonular fibres that hold the lens.
- Holds TGF-β in a latent form in the matrix; when fibrillin fails, TGF-β signalling rises in the aortic wall.
- Dominant FBN1 variants cause Marfan syndrome: aortic root dilation, upward lens dislocation and tall stature with long limbs.
- Also called
- FBN1, Microfibrils
- Genes
- FBN1
- Structure (PDB)
- 1UZJ
Structure
- Structure 1UZJ is a human fibrillin-1 fragment (cbEGF22–TB4–cbEGF23) with calcium ions; calcium stiffens the cbEGF domains.
- The TB4 domain of this fragment carries the RGD sequence that binds cell integrins.
Regulation
- Secreted by fibroblasts, smooth-muscle cells and lens cells; assembled into microfibrils outside the cell.
- Many Marfan variants change a cysteine or a calcium-binding residue, so the domain misfolds or is degraded early.
Inhibitors and toxins
- Loss of calcium from cbEGF domains (more protease-sensitive)
- Dominant-negative FBN1 variants
Clinical notes
- Marfan syndrome: risk of aortic dissection; the aortic root is followed by echocardiography and blood pressure is controlled.
- Lens dislocation in Marfan is typically upward (in homocystinuria, downward).
- FBN1 variants also cause short-stature dysplasias with thick skin (acromicric and geleophysic dysplasia).
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
Which gene is altered in Marfan syndrome?
FBN1, which encodes fibrillin-1; inheritance is autosomal dominant.
Why does loss of fibrillin-1 harm the aorta beyond weakening it?
Fibrillin holds latent TGF-β; without it TGF-β signalling rises, which degrades the wall and dilates the aortic root.
Which way does the lens dislocate in Marfan syndrome?
Upward and outward, because the fibrillin zonular fibres break; in homocystinuria it usually goes downward.
Which ion stabilises fibrillin's cbEGF domains?
Calcium; without it the domains become floppy and are degraded more easily.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: FBN1: Fibrillin-1 (human) (UniProt, 2026); FBN1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Marfan syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1UZJ: Integrin binding cbEGF22-TB4-cbEGF33 fragment of human fibrillin-1, holo form. (RCSB Protein Data Bank, 2026); Elastic fibre formation (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.