Fig. 4
From: Expanding the clinical spectrum of COL1A1 mutations in different forms of glaucoma
Structural effect of detected mutations in COL1A1. a Gly154 is located in a regular triple-helical collagen segment. The two glycines belonging to the COL1A1-chains are shown in space-filled presentation and are labelled. b In the Gly154Val variant, the larger valine sidechain cannot be accommodated at this sequence positions resulting in several severe clashes with the adjacent amino acids (indicated by black arrows). c Gly767 is located in a triple-helical collagen segment. The two glycines belonging to the COL1A1-chains are shown in space-filled presentation and are labelled. d In the Gly767Ser variant, the larger serine sidechain cannot be accommodated at this sequence positions resulting in several severe clashes with the adjacent amino acids (indicated by black arrows). e Met264 belongs to a stretch of COL1A1 that is recognized by fibronectin. Met264 forms tight sidechain packing interactions with Trp553 of fibronectin. Both residues are shown in space-filled presentation; the remaining residues of COL1A1 are shown in stick presentation (atom-type coloring) and fibronectin is shown as blue ribbon. f In the Met264Leu variant, the Cγ-branched leucine sidechain forms steric clashes (black arrow) with Trp553, which are expected to decrease binding affinity. g Ala1083 is located immediately adjacent to Arg1084, which confers the consensus of a high-affinity recognition site for the chaperone Hsp47 that is essential for the proper assembly of the triple-helical procollagen molecules. The collagen triple-helix is shown in red, green, and blue; the two bound Hsp47 molecules are depicted in blue and cyan. Arg1084 of collagen and Asp385 of Hsp47 form a salt-bridge that is crucial for high-affinity binding. The residues are shown in stick and their interaction is highlighted by an orange circle. Ala1083 of collagen forms a weak sidechain interaction with Leu381 of Hsp47 (residues in space-filled presentation). h In the Ala1083Thr variant, the bulkier threonine sidechain causes steric clashes with Leu381 (black arrow). Further, Ala1083 sidechain hydroxyl group is positioned close to Arg1084 (orange arrow), which might interfere with the Arg1084-Asp385 hydrogen bond. Both effects are expected to decrease the collagen-Hsp47 interaction