Surreal digital illustration of collagen type III at high resolution

The Collagen Comeback: How Type III is Revolutionizing Skin Health and Beyond

Avery Sinclair in Science & Nature June 2025 • 4 min read.

"Unlocking the secrets of human collagen type III: From high-resolution structures to potent cell adhesion, discover the breakthrough that could redefine regenerative medicine."

Collagen, the most abundant protein in the animal kingdom, serves as the very scaffolding upon which our bodies are built. It's the key structural component of everything from our skin and tendons to our ligaments and bones. Within this diverse family of proteins, collagen type III (hCOL3A1) stands out for its unique role and distribution in the body.

Human collagen type III is a fibril-forming collagen predominantly found in extensible connective tissues like the skin, vascular system, and internal organs. More than just a structural component, hCOL3A1 is critically involved in vital processes such as wound healing, the formation of collagen fibrils, and maintaining cardiovascular health. Its importance in tissue repair and maintenance makes it a prime target for regenerative medicine and biomaterial development.

Recent research has focused on the charged residues within hCOL3A1, which are believed to be vital for collagen binding and recognition. Scientists have discovered that a specific triple-helix fragment of hCOL3A1, known as Gly489-Gly510, contains multiple charged residues and charged triplets, making it a region of significant interest. This discovery has paved the way for high-resolution structural analysis and the development of innovative applications.

Decoding the Structure: A High-Resolution Breakthrough

Surreal digital illustration of collagen type III at high resolution

A team of researchers has successfully solved the crystal structure of the Gly489-Gly510 fragment of hCOL3A1 at a high resolution of 1.50 Å. This breakthrough provides unprecedented insights into the conformation of the triple-helix region, revealing critical details about its stability and potential interactions. The study identified strong interchain and interhelical hydrogen bonds, as well as flexible bending within the triple helix, all of which contribute to its unique properties.

The high-resolution structure revealed that the Arg491 residues in the triple helix form strong hydrogen bonds, creating a unique “arginine triangle” that stabilizes the helix. Furthermore, the Gly489-Gly501 region exhibits a bend of 15.12°, suggesting that this segment has significant flexibility. This flexibility may be crucial for interactions with other molecules, such as integrins, which are essential for cell adhesion.

High-Resolution Imaging: Visualizing collagen structure at 1.50 Å.
Hydrogen Bonds: Detailed mapping of interchain support.
Helix Flexibility: Observing Gly489-Gly501 bending for cell interaction.

To explore the functional implications of these structural features, the researchers synthesized collagen peptides around the Gly489-Gly510 region. These peptides exhibited potent cell adhesion activities, mediated by integrin interactions. In a significant advancement, the team developed a method to produce a recombinant protein, T16, consisting of 16 tandem repeats of the Gly483-Pro512 fragment of hCOL3A1. The T16 protein displayed strong cell adhesion activity without causing cytotoxicity, making it a promising candidate for biomaterial applications.

The Future of Collagen Type III: New Horizons in Medicine and Materials

The detailed structural insights and functional characterization of hCOL3A1’s Gly489-Gly510 region pave the way for exciting new applications in regenerative medicine and biomaterials. The T16 recombinant protein, with its strong cell adhesion activity and lack of cytotoxicity, holds immense potential for developing advanced wound healing therapies, tissue engineering scaffolds, and targeted drug delivery systems. By harnessing the unique properties of collagen type III, scientists are opening up new possibilities for repairing and regenerating tissues, with potential benefits for millions worldwide.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.bbrc.2018.12.018, Alternate LINK

Title: Characterization By High-Resolution Crystal Structure Analysis Of A Triple-Helix Region Of Human Collagen Type Iii With Potent Cell Adhesion Activity

Subject: Cell Biology

Journal: Biochemical and Biophysical Research Communications

Publisher: Elsevier BV

Authors: Chen Hua, Yun Zhu, Wei Xu, Sheng Ye, Rongguang Zhang, Lu Lu, Shibo Jiang

Published: 2019-01-01

Everything You Need To Know

What is human collagen type III (hCOL3A1), and what makes it significant in the context of regenerative medicine?

Human collagen type III, or hCOL3A1, is a type of fibril-forming collagen found predominantly in extensible connective tissues such as the skin, vascular system, and internal organs. It plays a crucial role in wound healing, the formation of collagen fibrils, and maintaining cardiovascular health. Recent research highlights a specific region within hCOL3A1, the Gly489-Gly510 fragment, for its charged residues and potential in collagen binding and recognition.

What key structural features were revealed by the high-resolution analysis of the Gly489-Gly510 fragment of hCOL3A1, and how do these features contribute to its function?

The high-resolution structure of the Gly489-Gly510 fragment of hCOL3A1 revealed key structural features such as strong interchain and interhelical hydrogen bonds. Specifically, the Arg491 residues form a unique “arginine triangle” that stabilizes the helix. Additionally, the Gly489-Gly501 region exhibits flexibility, which is crucial for interactions with other molecules like integrins, essential for cell adhesion. This detailed understanding aids in designing targeted therapies and biomaterials.

What is the T16 recombinant protein, and why is it considered a promising candidate for biomaterial applications?

The T16 recombinant protein is composed of 16 tandem repeats of the Gly483-Pro512 fragment of hCOL3A1. It's significant because it exhibits strong cell adhesion activity without causing cytotoxicity. This makes it a promising candidate for various biomaterial applications, including advanced wound healing therapies, tissue engineering scaffolds, and targeted drug delivery systems, potentially revolutionizing regenerative medicine.

What are the potential applications and implications of the structural insights into hCOL3A1 and the development of the T16 protein for future medical treatments?

The discovery of the high-resolution structure of the Gly489-Gly510 fragment and the development of the T16 protein could lead to more effective treatments for chronic wounds, improved tissue regeneration in damaged organs, and novel drug delivery systems that target specific cells or tissues. The insights gained from studying hCOL3A1 can also inspire the design of new biomaterials with enhanced biocompatibility and functionality.

What aspects of collagen research are not covered in the study of hCOL3A1's Gly489-Gly510 region, and why is it important to consider these broader contexts?

While the research focuses on the Gly489-Gly510 region and the T16 protein of hCOL3A1, other regions of the collagen molecule and other types of collagen also play significant roles in tissue structure and function. Further research is needed to fully understand the interactions between different collagen types, the influence of post-translational modifications, and the impact of genetic variations on collagen-related diseases. Understanding the broader context of collagen biology is crucial for developing comprehensive therapeutic strategies.