In-depth correlation analysis demonstrates that 4-hydroxyproline at the Yaa position of Gly-Xaa-Yaa repeats dominantly stabilizes collagen triple helix

Taga, Yuki; Tanaka, Keisuke; Hattori, Shunji

doi:10.1016/j.mbplus.2021.100067

Cited by 20 publications

(13 citation statements)

References 35 publications

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“…The 4Hyp content hardly differs depending on the collagen source since this major form of Hyp is essential for maintaining the thermal stability of collagen 42 , 43 . In contrast, the 3Hyp content dramatically varies with the tissue, species, and collagen type, although its biological role has remained unclear 25 .…”

Section: Discussionmentioning

confidence: 99%

“…This result suggests that selecting other sources containing further larger amounts of 3Hyp leads to more high absorption of Gly-3Hyp-4Hyp comparable or surpassing that of Pro-4Hyp. We recently analyzed collagens from various species and showed that the 3Hyp content is particularly high in invertebrate collagens 43 , which can be candidates for the source to prepare Gly-3Hyp-4Hyp-rich collagen hydrolysate.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

et al. 2022

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There are increasing reports demonstrating high bioavailability of 4-hydroxyproline (4Hyp)-containing oligopeptides after oral ingestion of collagen hydrolysate and their bioactivity. In contrast, no study investigates the fate of another collagen-specific but minor amino acid, 3Hyp. Here, we identified Gly-3Hyp-4Hyp tripeptide in human blood at high concentrations, comparable to other 4Hyp-containing oligopeptides, after ingesting porcine skin collagen hydrolysate. Additionally, Gly-3Hyp-4Hyp uniquely maintained the maximum concentration until 4 h after the ingestion due to its exceptionally high resistance to peptidase/protease demonstrated by incubation with mouse plasma. In mice, oral administration of collagen hydrolysate prepared from bovine tendon, which contains a higher amount of 3Hyp, further increased blood Gly-3Hyp-4Hyp levels compared to that from bovine skin. Furthermore, Gly-3Hyp-4Hyp showed chemotactic activity on skin fibroblasts and promoted osteoblast differentiation. These results highlight the specific nature of the Gly-3Hyp-4Hyp tripeptide and its potential for health promotion and disease treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

et al. 2022

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“…Another consideration is that 4-Hyp reduces the number of conformations available to the random coil of triple helix [34]. The latest update on the current understanding of this effect is summarized by Taga and colleagues [35].…”

Section: Hyp In Collagenmentioning

confidence: 99%

Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment

Belostotsky¹,

Frishberg²

2022

IJMS

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Hydroxyproline is one of the most prevalent amino acids in animal proteins. It is not a genetically encoded amino acid, but, rather, it is produced by the post-translational modification of proline in collagen, and a few other proteins, by prolyl hydroxylase enzymes. Although this post-translational modification occurs in a limited number of proteins, its biological significance cannot be overestimated. Considering that hydroxyproline cannot be re-incorporated into pro-collagen during translation, it should be catabolized following protein degradation. A cascade of reactions leads to production of two deleterious intermediates: glyoxylate and hydrogen peroxide, which need to be immediately converted. As a result, the enzymes involved in hydroxyproline catabolism are located in specific compartments: mitochondria and peroxisomes. The particular distribution of catabolic enzymes in these compartments, in different species, depends on their dietary habits. Disturbances in hydroxyproline catabolism, due to genetic aberrations, may lead to a severe disease (primary hyperoxaluria), which often impairs kidney function. The basis of this condition is accumulation of glyoxylate and its conversion to oxalate. Since calcium oxalate is insoluble, children with this rare inherited disorder suffer from progressive kidney damage. This condition has been nearly incurable until recently, as significant advances in substrate reduction therapy using small interference RNA led to a breakthrough in primary hyperoxaluria type 1 treatment.

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“…We also looked for correlations between the locations of the imino acid within the (Gly-X-Y) triplet and the flexibility. This is because most prolines in the Y position are 4-hydroxylated (while most in the X position are not, with a small fraction 3-hydroxylated) (61,(80)(81)(82). Hydroxyproline increases the thermal stability of the triple helix (83,84), and we thus wished to determine if its presence correlated with increased triple-helix bending rigidity.…”

Section: Triple Helix Mechanical Inhomogeneity: Collagen IIImentioning

confidence: 99%

Sequence-dependent mechanics of collagen reflect its structural and functional organization

Al-Shaer¹,

Lyons²,

Ishikawa

et al. 2020

Preprint

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Extracellular matrix mechanics influence diverse cellular functions, yet surprisingly little is known about the mechanical properties of their constituent collagens. In particular, network-forming collagen IV, an integral component of basement membranes, has been far less studied than fibril-forming collagens. A key feature differentiating collagen IV is the presence of interruptions in the triple-helix-defining (Gly-X-Y) sequence along its collagenous domain. Here, we used atomic force microscopy (AFM) to determine the impact of these interruptions on the flexibility of collagen. Our extracted flexibility profile reveals that collagen IV possesses highly heterogeneous mechanics, ranging from semi-flexible regions as found for fibril-forming collagens to a lengthy region of high flexibility towards its N terminus. A simple model in which flexibility is dictated only by the presence of interruptions fit the extracted profile reasonably well, providing insight into the alignment of chains and supporting the role of interruptions in instilling flexibility. However, limitations of this model were illuminated by our determination of variable flexibility along continuously triple-helical collagen III, which we found to possess a high-flexibility region around its matrix-metalloprotease (MMP) binding site. Surprisingly, proline content did not correlate with local flexibility in either collagen type. We also found that physiologically relevant changes in pH and chloride concentration did not alter the flexibility of collagen IV, indicating such environmental changes are not used to control its compaction during secretion. Although extracellular chloride ions play a role in triggering collagen IV network formation, they do not appear to modulate the structure of its collagenous domain.

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In-depth correlation analysis demonstrates that 4-hydroxyproline at the Yaa position of Gly-Xaa-Yaa repeats dominantly stabilizes collagen triple helix

Cited by 20 publications

References 35 publications

Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment

Sequence-dependent mechanics of collagen reflect its structural and functional organization

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