Co- ja posttranslationaalinen proliinihydroksylaatio kollageenissa (2019)

https://www.ncbi.nlm.nih.gov/pubmed/31350381

Essays Biochem. 2019 Sep 13;63(3):325-335. doi: 10.1042/EBC20180053. Print 2019 Sep 13.

Role of prolyl hydroxylation in the molecular interactions of collagens.

Rappu P¹, Salo AM², Myllyharju J², Heino J³.

1

Department of Biochemistry, University of Turku, FI-20014, Finland.

2

Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu FI-90014, Finland.

3

Department of Biochemistry, University of Turku, FI-20014, Finland jyrki.heino@utu.fi.

Abstract

Co- and post-translational hydroxylation of proline residues is critical for the stability of the triple helical collagen structure. In this review, we summarise the biology of collagen prolyl 4-hydroxylases and collagen prolyl 3-hydroxylases, the enzymes responsible for proline hydroxylation. Furthermore, we describe the potential roles of hydroxyproline residues in the complex interplay between collagens and other proteins, especially integrin and discoidin domain receptor type cell adhesion receptors. Qualitative and quantitative regulation of collagen hydroxylation may have remarkable effects on the properties of the extracellular matrix and consequently on the cell behaviour.

© 2019 The Author(s).

KEYWORDS:
collagen; extracellular matrix; integrins; molecular interactions; prolyl hydroxylase

PMID:

31350381

PMCID:

PMC6744578

DOI:

10.1042/EBC20180053

Free PMC Article

• Introduction

  The members of the large collagen family have characteristic domains with a triple-helical structure formed by three collagen α chains. Special features in the primary α chain structure enable the formation of the collagenous triple helix. These include the location of glycine as every third residue and the presence of co- and post-translationally hydroxylated proline residues [1].
  Proline residues are hydroxylated by three isoenzymes forming the group of collagen prolyl 4-hydroxylases (C-P4Hs) (Figure 1). In addition to abundant 4-hydroxyproline (4-Hyp) residues, collagens also harbour few 3-hydroxyprolines (3-Hyp) [2] (Figure 2). Specific collagen prolyl 3-hydroxylases (C-P3Hs) are responsible for this modification.
  
  
   The melting temperature of collagenous triple helix is directly proportional to the 4-Hyp content [3,4]. Thus, prolyl 4-hydroxylation is critical for the stability of the individual tropocollagen molecules. Collagens are known to have numerous interaction partners that can recognise triple-helical motifs in collagens [5]. Here, we review the many putative roles of prolyl 4-hydroxylation in the molecular interactions of collagen including fibril formation (Figure 3). We also introduce the collagen receptor subgroup of the integrin superfamily [6,7]. The structural basis of the interaction of the integrin type adhesion receptors with collagens has been unveiled in detail and their typical recognition sites often contain 4-Hyp residues [8,9], although there are also some exceptions [10,11]. Furthermore, another group of cellular collagen receptors, formed by discoidin domain receptors 1 and 2 (DDR1 and DDR2), also recognises a 4-Hyp containing motif [12]. Finally, we discuss the potential physiological significance of direct cell adhesion to collagens.