Ziploc-ing the structure: Triple helix formation is coordinated by rough endoplasmic reticulum resident PPIases

• Published in: Biochimica et biophysica acta Vol. 1850; no. 10; pp. 1983 - 1993
• Main Authors: Ishikawa, Yoshihiro, Boudko, Sergei, Bächinger, Hans Peter
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2015
• Subjects: Animals; biosynthesis; catalysts; Collagen; Collagen - biosynthesis; drugs; Endoplasmic Reticulum - metabolism; Humans; Molecular chaperone; molecular chaperones; Peptidyl prolyl cis/trans isomerase; peptidylprolyl isomerase; Peptidylprolyl Isomerase - metabolism; proline; Protein Folding; protein secretion; Protein Structure, Secondary; Protein–protein interaction; Rough endoplasmic reticulum; Protein folding; Peptidyl prolyl cis/trans isomerase; Rough endoplasmic reticulum; Collagen; Molecular chaperone; Protein–protein interaction
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2014.12.024

Protein folding is crucial for proteins' specific functions and is facilitated by various types of enzymes and molecular chaperones. The peptidyl prolyl cis/trans isomerases (PPIase) are one of these families of enzymes. They ubiquitously exist inside the cell and there are eight PPIases in the rough endoplasmic reticulum (rER), a compartment where the folding of most secreted proteins occurs. We review the functional and structural aspects of individual rER resident PPIases. Furthermore, we specifically discuss the role of these PPIases during collagen biosynthesis, since collagen is the most abundant protein in humans, is synthesized in the rER, and contains a proportionally high number of proline residues. The rER resident PPIases recognize different sets of substrates and facilitate their folding. Although they are clearly catalysts for protein folding, they also have more broad and multifaceted functions. We propose that PPIases coordinate collagen biosynthesis in the rER. This review expands our understanding of collagen biosynthesis by explaining the influence of novel indirect mechanisms of regulating folding and this is also explored for PPIases. We also suggest future directions of research to obtain a better understanding of collagen biosynthesis and functions of PPIases in the rER. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets. •Collagen triple helix formation is catalyzed by rER resident PPIases.•Two cyclophilins and six FKBPs exist in the rER.•These PPIases act as enzymes, molecular chaperones or co-factors in the rER.•These proteins coordinate collagen folding.