Featured Research

from universities, journals, and other organizations

A step towards the prevention of collagen-related diseases

Date:
October 1, 2012
Source:
CNRS (Délégation Paris Michel-Ange)
Summary:
Scientists have just determined the three-dimensional structure of a key region of the procollagen molecule, the precursor form of collagen, the most abundant protein in the body. This region, called the C-propeptide domain, plays an extremely important role in collagen assembly, defects in which can lead to serious, often lethal diseases.

Three dimensional structure of the trimeric form of the C-propeptides of human procollagen. Each of the three strands is represented in different color.
Credit: © Bourhis et al.

A collaboration between groups from France and the UK, led by researchers from the Institut de Biologie et Chimie des Protéines (CNRS/Université Claude Bernard Lyon 1), have just determined the three-dimensional structure of a key region of the procollagen molecule, the precursor form of collagen, the most abundant protein in the body. This region, called the C-propeptide domain, plays an extremely important role in collagen assembly, defects in which can lead to serious, often lethal diseases.

This work is published on the 23 September 2012 in the journal Nature Structural and Molecular Biology.

Collagens make up a quarter of all protein mass in the body, where their role is to provide structural and functional integrity to all tissues and organs. As the major component of the extracellular matrix, these proteins are essential for the formation of several tissues, including skin, cornea, bone, cartilage, lungs and the cardiovascular system. However, excessive amounts of collagen deposition, or mutations in collagen genes, can result in numerous severe diseases.

Collagen precursor molecules consist of three procollagen strands that are synthesized then subsequently assemble within the cell. These molecules are then secreted into the extracellular matrix where, following a process of maturation, they themselves assemble to form long collagen fibers. These two processes, assembly of the molecule and assembly of the fiber, are both controlled by the C-propeptide, a domain consisting of 245 amino acids and found at the end of each procollagen strand. Mutations in procollagen genes, including the C-propeptide region, result in numerous pathologies, often lethal, such as osteogenesis imperfecta or chondrodysplasias (1).

In order to design new therapeutic strategies and to better understand the mechanism of action of the C-propeptide, the researchers (2) have determined its three-dimensional structure, by X-ray crystallography. This has enabled them to map the numerous mutations present in the C-propeptides of the different genetic types of procollagen and to correlate this information with the severity of the associated diseases. Thus the 3D structure could become a prognostic tool for predicting a priori the consequences of such mutations.

Knowledge of the 3D structure of this domain could also make it possible in the future to control the formation of collagen fibers in the extracellular matrix. In order for these fibers to form, the C-propeptides must first be removed from the rest of the molecule by specific enzymes. Therefore, if one could prevent or slow down the removal of the C-propeptide, the production of collagen fibers could also be reduced. In addition, a better understanding of the mechanism of action of the C-propeptide could help to prevent the association of the three procollagen strands within the cell. Such strategies could thus prevent the many different kinds of fibrosis, a group of serious and often fatal disorders that result from an excessive accumulation of collagen in several organs including the heart, kidneys, liver and lungs.

This work, supported by the Fondation de France and by the French National Research Agency, represents an important step towards the development of therapeutic molecules and is also the subject of a patent application.

(1) Disorders of bone and cartilage development that result in skeletal malformations

(2) Laboratories: Tissue biology and therapeutic engineering (CNRS/Université Claude Bernard Lyon 1), Structural and molecular basis of infectious diseases (CNRS/Université Claude Bernard Lyon 1), Unit for virus host cell interactions (CNRS/Université Joseph Fourier/EMBL,Grenoble), Wellcome Trust Centre for Human Genetics (University of Oxford).


Story Source:

The above story is based on materials provided by CNRS (Délégation Paris Michel-Ange). Note: Materials may be edited for content and length.


Journal Reference:

  1. Jean-Marie Bourhis, Natacha Mariano, Yuguang Zhao, Karl Harlos, Jean-Yves Exposito, E Yvonne Jones, Catherine Moali, Nushin Aghajari, David J S Hulmes. Structural basis of fibrillar collagen trimerization and related genetic disorders. Nature Structural & Molecular Biology, 2012; DOI: 10.1038/nsmb.2389

Cite This Page:

CNRS (Délégation Paris Michel-Ange). "A step towards the prevention of collagen-related diseases." ScienceDaily. ScienceDaily, 1 October 2012. <www.sciencedaily.com/releases/2012/10/121001095519.htm>.
CNRS (Délégation Paris Michel-Ange). (2012, October 1). A step towards the prevention of collagen-related diseases. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/10/121001095519.htm
CNRS (Délégation Paris Michel-Ange). "A step towards the prevention of collagen-related diseases." ScienceDaily. www.sciencedaily.com/releases/2012/10/121001095519.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) — A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) — The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) — Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:  

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile iPhone Android Web
          Follow Facebook Twitter Google+
          Subscribe RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins