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. Author manuscript; available in PMC: 2014 Aug 1.
Published in final edited form as: Hum Mutat. 2013 May 28;34(8):1075–1079. doi: 10.1002/humu.22351

Figure 2. Protein Domain and Structure analysis.

Figure 2

a. Nidogen1 domains. A stop codon leads to deletion of the Nidogen1 G2 beta barrel domain (green), several EGF-like domains (blue), and the thyroglobulin Type-1 domain.

b. LamininC1 domains. The family-2 mutation was found in EGF-6-like (blue asterisk). There are 11 EGF-like domains (blue), and a previously known interaction with Nidogen-1 occurs through EGF-8-like domain (grey asterisk).

c. Ortholog alignment shows high evolutionary conservation of the Threonine-746 residue (red box).

d. Paralog alignment of three human EGF-6-like domains from LAMC1, C2, and C3 shows size conservation of the 746-residue, Threonine (M.W. 119 Da) and Valine (M.W. 117 Da, red box).

e. The normal threonine-746 (red) occupies a small space between rigid cysteine disulfide bridges (orange), and a mutation to methionine leads to steric interference with surrounding residues (blue).

f. EGF-like-6 domain (homology model in blue) shows 33% sequence identity to EGF-like-8 domain (grey), which interacts with the Nidogen1 G2 beta barrel domain (green). The mutation is expected to disrupt a beta sheet (red).