Figure 1. Diagram of a calcium-binding epidermal growth factor-like module (cbEGF). Fibrillin-1 contains 43 cbEGF modules, which comprise about 42 amino acid residues with six cysteine residues (C) which together form three disulfide bonds in a 1–3, 2–4, 5–6 arrangement. cbEGF modules additionally contain a calcium-binding consensus: D/N–X–D/N–E/Q–X_m–D/N*–X_n–Y/F (where m and n are variable and * indicates potential beta hydroxylation). (Figure modified from Robinson PN and Booms P (2001) Cellular and Molecular Life Sciences 58: 1698–1707.)

Figure 2. Domain organization of fibrillin-1. Fourteen putative N-glycosylation sites are shown as black dots above the protein, N- and C-terminal proteolytic processing sites are shown as arrows and an RGD motif cell-attachment signal is shown as an open triangle. EGF: epidermal growth factor; cbEGF: calcium-binding epidermal growth factor-like module; LTBP: latent transforming growth factor 1 binding protein (module also referred to as the TGF1bp). (Figure modified from Robinson PN and Booms P (2001) Cellular and Molecular Life Sciences 58: 1698–1707.)

Figure 3. Proposed dominant negative model of the pathogenesis of Marfan syndrome. Top: wild-type (wt) fibrillin-1 monomers polymerize with one another and with a series of other proteins to form aggregate structures called microfibrils. Bottom: a missense mutation (represented as an asterisk) is likely to alter the conformation of affected fibrillin-1 monomers, which could interfere with polymerization, destabilize the polymeric microfibrils causing a progressive loss of microfibrils or otherwise interfere with proper microfibrillar function. (Figure modified from Robinson PN and Booms P (2001) Cellular and Molecular Life Sciences 58: 1698–1707.)