Conformational Effects of Gly–X–Gly Interruptions in the Collagen Triple Helix

Bella, Jordi; Liu, Jingsong; Kramer, Rachel Z; Brodsky, Barbara; Berman, Helen M.

doi:10.1016/j.jmb.2006.07.014

Cited by 65 publications

(66 citation statements)

References 52 publications

(101 reference statements)

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“…Early post-translational modification includes hydroxylation and glycosylation. The presence of the non-helical domains associated with each collagen, the propeptide domains at the C-and N-terminals [26] play an important role in the collagen triple helical formation [27] (Fig. 7, Step 1).…”

Section: Discussionmentioning

confidence: 99%

Premature Collagen Fibril Formation, Fibroblast-Mast Cell Interactions and Mast Cell-Mediated Phagocytosis of Collagen in Keloids

Arbi

Eksteen

Oberholzer

et al. 2015

Ultrastructural Pathology

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Keloids are benign hyper-proliferative growths of fibrous tissue, where increased fibroblast activity results in abnormal collagen deposition. Excessive inflammation is a characteristic feature of keloids but little is known about the underlying ultrastructural features of keloids related to collagen processing, fibril and fibre formation, the interaction between fibroblasts and associated collagen fibres and mast cells. In this study, the ultrastructure of the dermis of keloid patients was evaluated using light and transmission electron microscopy techniques. Abnormal intracellular premature collagen fibril formation was observed. Phagocytosis of collagen fibrils by mast cells was a common ultrastructural feature of keloid tissue as was a close or direct 2 association between fibroblasts and mast cells. Based on these findings and recent advances in knowledge related to collagen synthesis, fibril formation and processing we hypothesise that keloid formation is primary due to abnormal collagen synthesis where the consequent accumulation of collagen fibres causes increased mast cell recruitment and collagen phagocytosis. Subsequent release of mast cell derived mediators then promotes further collagen synthesis. The observation of early formation in keloid tissue of premature insoluble collagen fibrils supports previous studies that enzymes such as procollagen C-proteinase are important early therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Premature Collagen Fibril Formation, Fibroblast-Mast Cell Interactions and Mast Cell-Mediated Phagocytosis of Collagen in Keloids

Arbi

Eksteen

Oberholzer

et al. 2015

Ultrastructural Pathology

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“…In the range of lengths studied here, the peptides containing longer interruptions (m ¼ 6, 7, 8, and 9) showed lower MRE 225nm values, lower Rpn values, and decreased calorimetric enthalpies compared with the peptides containing the shorter interruptions (m ¼ 1, 3, 4, and 5). It is likely that the shorter interruption peptides contain very localized perturbation of dihedral angles and hydrogen bonding as seen in molecular structures of peptides with 1-and 4-residue interruptions [15][16][17] and with a Gly to Ala replacement equivalent to a 5-residue interruption. 29 The increased conformational perturbation associated with longer interruptions could arise from greater deviation from the standard triple-helix or disruption of a larger segment of the molecule.…”

Section: Discussionmentioning

confidence: 99%

“…The perturbations caused by 1-and 4-residue imperfections have been characterized in model peptides by X-ray crystallography and NMR spectroscopy. [15][16][17] These triple-helical peptides show distortion in dihedral angles and perturbed hydrogen bonding localized to the interruption site. In addition, the twist of the superhelix on one end of the peptide is out of register with the other end.…”

Section: Introductionmentioning

confidence: 99%

Interruptions in the collagen repeating tripeptide pattern can promote supramolecular association

Hwang¹,

Thiagarajan²,

Parmar³

et al. 2010

Protein Science

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The standard collagen triple-helix requires a perfect (Gly-Xaa-Yaa) n sequence, yet all nonfibrillar collagens contain interruptions in this tripeptide repeating pattern. Defining the structural consequences of disruptions in the sequence pattern may shed light on the biological role of sequence interruptions, which have been suggested to play a role in molecular flexibility, collagen degradation, and ligand binding. Previous studies on model peptides with 1-and 4-residue interruptions showed a localized perturbation within the triple-helix, and this work is extended to introduce natural collagen interruptions up to nine residue in length within a fixed (Gly-Pro-Hyp) n peptide context. All peptides in this set show decreases in triple-helix content and stability, with greater conformational perturbations for the interruptions longer than five residue. The most stable and least perturbed structure is seen for the 5-residue interruption peptide, whose sequence corresponds to a Gly to Ala missense mutation, such as those leading to collagen genetic diseases. The triple-helix peptides containing 8-and 9-residue interruptions exhibit a strong propensity for self-association to fibrous structures. In addition, a small peptide modeling only the 9-residue sequence within the interruption aggregates to form amyloid-like fibrils with antiparallel b-sheet structure. The 8-and 9-residue interruption sequences studied here are predicted to have significant cross-b aggregation potential, and a similar propensity is reported for 10% of other naturally occurring interruptions. The presence of amyloidogenic sequences within or between triple-helix domains may play a role in molecular association to normal tissue structures and could participate in observed interactions between collagen and amyloid.

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“…Model peptides based on the Gly-X-Gly deletions of Type VIII collagen have been shown by X-ray crystallography to align into layers with the deleted regions lined up (Bella et al, 2006). This is very reminiscent of the smectic ordering of preCols seen in byssal threads by atomic force microscopy (AFM) (Hassenkam et al, 2004).…”

Section: Collagen Domainmentioning

confidence: 90%

Holdfast heroics: comparing the molecular and mechanical properties ofMytilus californianusbyssal threads

Harrington

Waite

2007

Journal of Experimental Biology

161

207

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The marine mussel Mytilus californianus Conrad inhabits the most wave-exposed regions of the rocky intertidal by dint of its extraordinary tenacity. Tenacity is mediated in large part by the byssus, a fibrous holdfast structure. M. californianus byssal threads, which are mechanically superior to the byssal threads of other mytilids, are composed almost entirely of a consortium of three modular proteins known as the preCols. In this study, the complete primary sequence of preCols from M. californianus was deduced and compared to that of two related species with mechanically inferior byssal threads, M. edulis Linnaeus and M. galloprovincialis Lamarck in order to explore structure-function relationships.The preCols from M. californianus are more divergent from the other two species than they are from one another. However, the degree of divergence is not uniform among the various domains of the preCols, allowing us to speculate on their mechanical role. For instance, the extra spider silklike runs of alanine-rich sequence in the flanking domains of M. californianus may increase crystalline order, enhancing strength and stiffness. Histidine-rich domains at the termini, in contrast, are highly conserved between species, suggesting a mechanical role common to all three. Mechanical testing of pH-treated and chemically derivatized distal threads strongly suggests that histidine side chains are ligands in reversible, metal-mediated crosslinks in situ. By combining the mechanical and sequence data, yield and self-healing in the distal region of threads have been modeled to emphasize the intricate interplay of enthalpic and entropic effects during tensile load and recovery.

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Conformational Effects of Gly–X–Gly Interruptions in the Collagen Triple Helix

Cited by 65 publications

References 52 publications

Premature Collagen Fibril Formation, Fibroblast-Mast Cell Interactions and Mast Cell-Mediated Phagocytosis of Collagen in Keloids

Premature Collagen Fibril Formation, Fibroblast-Mast Cell Interactions and Mast Cell-Mediated Phagocytosis of Collagen in Keloids

Interruptions in the collagen repeating tripeptide pattern can promote supramolecular association

Holdfast heroics: comparing the molecular and mechanical properties ofMytilus californianusbyssal threads

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