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Type I and type V procollagen triple helix uses different subsets of the molecular ensemble for lysine posttranslational modifications in the rER
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Collagen is the most abundant protein in humans. It has a characteristic triple-helix structure and is heavily posttranslationally modified. The complex biosynthesis of collagen involves processing by many enzymes and chaperones in the rough endoplasmic reticulum. Lysyl hydroxylase 1 (LH1) is required to hydroxylate lysine for cross-linking and carbohydrate attachment within collagen triple helical sequences. Additionally, a recent study of prolyl 3-hydroxylase 3 (P3H3) demonstrated that this enzyme may be critical for LH1 activity; however, the details surrounding its involvement remain unclear. If P3H3 is an LH1 chaperone that is critical for LH1 activity, P3H3 and LH1 null mice should display a similar deficiency in lysyl hydroxylation. To test this hypothesis, we compared the amount and location of hydroxylysine in the triple helical domains of type V and I collagen from P3H3 null, LH1 null, and wild-type mice. The amount of hydroxylysine in type V collagen was reduced in P3H3 null mice, but surprisingly type V collagen from LH1 null mice contained as much hydroxylysine as type V collagen from wild-type mice. In type I collagen, our results indicate that LH1 plays a global enzymatic role in lysyl hydroxylation. P3H3 is also involved in lysyl hydroxylation, particularly at cross-link formation sites, but is not required for all lysyl hydroxylation sites. In summary, our study suggests that LH1 and P3H3 likely have two distinct mechanisms to recognize different collagen types and to distinguish cross-link formation sites from other sites in type I collagen.
- Subjects :
- Male
collagen
0301 basic medicine
Protein Conformation
Lysine
CRTAP, cartilage-associated protein
lysyl hydroxylase
rER, rough endoplasmic reticulum
GGHL, glucosylgalactosyl hydroxylysine
Hydroxylysine
Biochemistry
Hydroxylation
Mice
chemistry.chemical_compound
SFM, serum-free media
Mice, Knockout
AAA, amino acid analysis
biology
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
molecular chaperone
ECM, extracellular matrix
endoplasmic reticulum
prolyl hydroxylase
posttranslational modifications
Endoplasmic Reticulum, Rough
Type I collagen
Research Article
Triple helix
Lysyl hydroxylase
Procollagen-Proline Dioxygenase
Collagen Type I
03 medical and health sciences
CypB, cyclophilin B
Animals
EDS, Ehlers–Danlos syndrome
Molecular Biology
LH 1, lysyl hydroxylase 1
030102 biochemistry & molecular biology
Endoplasmic reticulum
Cell Biology
Mice, Inbred C57BL
Procollagen peptidase
030104 developmental biology
chemistry
biology.protein
P3H3, prolyl 3-hydroxylase 3
PTM, posttranslational modification
Collagen Type V
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 296
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....963794e96db27b45cf8823e1b8528806