Structural Analysis of Type III Collagen Using Two Dimensional Nuclear Magnetic Resonance

Headnote

Type III collagen belongs to one of the twenty-eight known collagen types. It is found throughout the body, including being a major component of blood vessels, internal organs, and skin. A collagen molecule comprises of over a thousand amino acids, which are all arranged in three left-handed peptide chains folded together into a characteristic right-handed triple helix. Type III collagen is known to play a role in wound healing and tissue repair, and is the cause for hereditary Ehlers-Danlos syndrome (EDS) type IV which often leads to ruptures of large arteries and internal organs and, in severe cases, death. However, due to the large size of its molecule, not much is known about how type III collagen's structure influences the functions it has in the body. Two-dimensional nuclear magnetic resonance (2D NMR) is a relatively new analytical technique that has become increasingly more utilized in the study of biological molecules, since it has the ability to detect relationships of atoms both through their bonds and through space. Still, because of the length and repetitive nature of its sequence, the best way to study the collagen molecule by NMR is with model peptide sequences that mimic a particular collagen segment of interest. This review summarizes the research conducted up to this point on collagens using nuclear magnetic resonance.

Keywords: collagen; collagen type III; 2D NMR; Ehlers-Danlos syndrome; collagen folding; Collagen NMR analysis.

Abbreviations: Ehlers-Danlos syndrome (EDS); Two-dimensional nuclear magnetic resonance (2D NMR); Fourier Transform (FT); one dimensional nuclear magnetic resonance (1D NMR); correlation spectroscopy (1H-1H COSY);total correlation spectroscopy (1H-1H TOCSY); heteronuclear single quantum correlation (HSQC); heteronuclear multiple quantum correlation (HMQC); heteronuclear multiple bond correlation (HMBC); Nuclear Overhauser effect spectroscopy (NOESY); rotational Overhauser effect spectroscopy(ROESY)

Introduction

Collagen is a fibrous protein that makes up close to a third of all protein in the body, and is found in connective tissues like bone, cartilage, tendons, skin, blood vessels, etc. [1]. It is a rigid, non-stretchable protein that enables running and jumping activities, and whose strength originates from the unique structure of peptides that organize in a triple helical conformation. The amino acid sequence of a basic structural unit of collagen, tropocollagen, includes approximately one thousand amino acids in each polypeptide chain, with the length of three hundred...