Differential Effects of Collagen Prolyl 3-Hydroxylation on Skeletal Tissues


Mutations in the genes encoding cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1) were the first identified causes of recessive Osteogenesis Imperfecta (OI). These proteins, together with cyclophilin B (encoded by PPIB), form a complex that 3-hydroxylates a single proline residue on the α1(I) chain (Pro986) and has cis/trans isomerase (PPIase) activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1H662A). This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I) and α1(II) collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase activity versus complete ablation of the prolyl 3-hydroxylation complex.


Vyšlo v časopise: Differential Effects of Collagen Prolyl 3-Hydroxylation on Skeletal Tissues. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004121
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004121

Souhrn

Mutations in the genes encoding cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1) were the first identified causes of recessive Osteogenesis Imperfecta (OI). These proteins, together with cyclophilin B (encoded by PPIB), form a complex that 3-hydroxylates a single proline residue on the α1(I) chain (Pro986) and has cis/trans isomerase (PPIase) activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1H662A). This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I) and α1(II) collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase activity versus complete ablation of the prolyl 3-hydroxylation complex.


Zdroje

1. RauchF, GlorieuxFH (2004) Osteogenesis imperfecta. Lancet 363: 1377–1385.

2. MorelloR, BertinTK, ChenY, HicksJ, TonachiniL, et al. (2006) CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127: 291–304.

3. IshikawaY, WirzJ, VrankaJA, NagataK, BachingerHP (2009) Biochemical characterization of the prolyl 3-hydroxylase 1.cartilage-associated protein.cyclophilin B complex. J Biol Chem 284: 17641–17647.

4. TiainenP, PasanenA, SormunenR, MyllyharjuJ (2008) Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV. J Biol Chem 283: 19432–19439.

5. VrankaJA, SakaiLY, BachingerHP (2004) Prolyl 3-hydroxylase 1: Enzyme characterization and identification of a novel family of enzymes. J Biol Chem 279: 23615–23621.

6. BaldridgeD, SchwarzeU, MorelloR, LenningtonJ, BertinTK, et al. (2008) CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat 29: 1435–1442.

7. BarnesAM, CarterEM, CabralWA, WeisM, ChangW, et al. (2010) Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. N Engl J Med 362: 521–528.

8. MariniJC, CabralWA, BarnesAM (2010) Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta. Cell Tissue Res 339: 59–70.

9. PyottSM, SchwarzeU, ChristiansenHE, PepinMG, LeistritzDF, et al. (2011) Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum Mol Genet 20: 1595–1609.

10. TakagiM, IshiiT, BarnesAM, WeisM, AmanoN, et al. (2012) A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence causes non-lethal osteogenesis imperfecta. PLoS One 7: e36809.

11. van DijkFS, NesbittIM, ZwikstraEH, NikkelsPG, PiersmaSR, et al. (2009) PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet 85: 521–527.

12. WillaertA, MalfaitF, SymoensS, GevaertK, KayseriliH, et al. (2009) Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation. J Med Genet 46: 233–241.

13. CabralWA, ChangW, BarnesAM, WeisM, ScottMA, et al. (2007) Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet 39: 359–365.

14. VrankaJA, PokidyshevaE, HayashiL, ZientekK, MizunoK, et al. (2010) Prolyl 3-hydroxylase 1 null mice display abnormalities in fibrillar collagen-rich tissues such as tendons, skin and bones. J Biol Chem 285: 17253–17262.

15. ChoiJW, SutorSL, LindquistL, EvansGL, MaddenBJ, et al. (2009) Severe osteogenesis imperfecta in cyclophilin B-deficient mice. PLoS Genet 5: e1000750.

16. ChangW, BarnesAM, CabralWA, BodurthaJN, MariniJC (2010) Prolyl 3-Hydroxylase 1 and CRTAP are Mutually Stabilizing in the Endoplasmic Reticulum Collagen Prolyl 3-Hydroxylation Complex. Hum Mol Genet 19: 223–234.

17. BaldridgeD, LenningtonJ, WeisM, HomanEP, JiangMM, et al. (2010) Generalized connective tissue disease in Crtap−/− mouse. PLoS One 5: e10560.

18. OzerA, BruickRK (2007) Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one? Nat Chem Biol 3: 144–153.

19. SiddiqA, AminovaLR, RatanRR (2007) Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress. Neurochem Res 32: 931–946.

20. HietaR, MyllyharjuJ (2002) Cloning and characterization of a low molecular weight prolyl 4-hydroxylase from Arabidopsis thaliana. Effective hydroxylation of proline-rich, collagen-like, and hypoxia-inducible transcription factor alpha-like peptides. J Biol Chem 277: 23965–23971.

21. PokidyshevaE, ZientekKD, IshikawaY, MizunoK, VrankaJA, et al. (2013) Posttranslational modifications in type I collagen from different tissues extracted from wild type and prolyl 3-hydroxylase 1 null mice. J Biol Chem 288: 24742–24752.

22. MizunoK, HayashiT, PeytonDH, BachingerHP (2004) The peptides acetyl-(Gly-3(S)Hyp-4(R)Hyp)10-NH2 and acetyl-(Gly-Pro-3(S)Hyp)10-NH2 do not form a collagen triple helix. J Biol Chem 279: 282–287.

23. JenkinsCL, BretscherLE, GuzeiIA, RainesRT (2003) Effect of 3-hydroxyproline residues on collagen stability. J Am Chem Soc 125: 6422–6427.

24. MizunoK, PeytonDH, HayashiT, EngelJ, BachingerHP (2008) Effect of the -Gly-3(S)-hydroxyprolyl-4(R)-hydroxyprolyl- tripeptide unit on the stability of collagen model peptides. Febs J 275: 5830–5840.

25. SchumacherMA, MizunoK, BachingerHP (2006) The crystal structure of a collagen-like polypeptide with 3(S)-hydroxyproline residues in the Xaa position forms a standard 7/2 collagen triple helix. J Biol Chem 281: 27566–27574.

26. OrgelJP, San AntonioJD, AntipovaO (2011) Molecular and structural mapping of collagen fibril interactions. Connect Tissue Res 52: 2–17.

27. EyreDR, WeisMA (2013) Bone Collagen: New Clues to Its Mineralization Mechanism from Recessive Osteogenesis Imperfecta. Calcif Tissue Int 93: 338–347.

28. MurshedM, McKeeMD (2010) Molecular determinants of extracellular matrix mineralization in bone and blood vessels. Curr Opin Nephrol Hypertens 19: 359–365.

29. BergRA, ProckopDJ (1973) The thermal transition of a non-hydroxylated form of collagen. Evidence for a role for hydroxyproline in stabilizing the triple-helix of collagen. Biochem Biophys Res Commun 52: 115–120.

30. HudsonDM, KimLS, WeisM, CohnDH, EyreDR (2012) Peptidyl 3-hydroxyproline binding properties of type I collagen suggest a function in fibril supramolecular assembly. Biochemistry 51: 2417–2424.

31. EhrlichH, DeutzmannR, BrunnerE, CappelliniE, KoonH, et al. (2010) Mineralization of the metre-long biosilica structures of glass sponges is templated on hydroxylated collagen. Nat Chem 2: 1084–1088.

32. DonoghuePC, SansomIJ, DownsJP (2006) Early evolution of vertebrate skeletal tissues and cellular interactions, and the canalization of skeletal development. J Exp Zool B Mol Dev Evol 306: 278–294.

33. BankRA, TekoppeleJM, JanusGJ, WassenMH, PruijsHE, et al. (2000) Pyridinium cross-links in bone of patients with osteogenesis imperfecta: evidence of a normal intrafibrillar collagen packing. J Bone Miner Res 15: 1330–1336.

34. LichtargeO, BourneHR, CohenFE (1996) An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol 257: 342–358.

35. LichtargeO, WilkinsA (2010) Evolution: a guide to perturb protein function and networks. Curr Opin Struct Biol 20: 351–359.

36. LuaRC, LichtargeO (2010) PyETV: a PyMOL evolutionary trace viewer to analyze functional site predictions in protein complexes. Bioinformatics 26: 2981–2982.

37. MihalekI, ResI, LichtargeO (2004) A family of evolution-entropy hybrid methods for ranking protein residues by importance. J Mol Biol 336: 1265–1282.

38. WilkinsA, ErdinS, LuaR, LichtargeO (2012) Evolutionary trace for prediction and redesign of protein functional sites. Methods Mol Biol 819: 29–42.

39. KutnerRH, ZhangXY, ReiserJ (2009) Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors. Nat Protoc 4: 495–505.

40. LiuP, JenkinsNA, CopelandNG (2003) A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res 13: 476–484.

41. MorelloR, BertinTK, SchlaubitzS, ShawCA, KakuruS, et al. (2008) Brachy-syndactyly caused by loss of Sfrp2 function. J Cell Physiol 217: 127–137.

42. ParfittAM, DreznerMK, GlorieuxFH, KanisJA, MallucheH, et al. (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2: 595–610.

43. VoideR, van LentheGH, MullerR (2008) Bone morphometry strongly predicts cortical bone stiffness and strength, but not toughness, in inbred mouse models of high and low bone mass. J Bone Miner Res 23: 1194–1203.

44. EyreD (1987) Collagen cross-linking amino acids. Methods Enzymol 144: 115–139.

45. MillerEJ (1972) Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry 11: 4903–4909.

46. EyreDR, MuirH (1975) The distribution of different molecular species of collagen in fibrous, elastic and hyaline cartilages of the pig. Biochem J 151: 595–602.

47. LaemmliUK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685.

48. HansonDA, EyreDR (1996) Molecular site specificity of pyridinoline and pyrrole cross-links in type I collagen of human bone. J Biol Chem 271: 26508–26516.

49. WuJJ, WoodsPE, EyreDR (1992) Identification of cross-linking sites in bovine cartilage type IX collagen reveals an antiparallel type II-type IX molecular relationship and type IX to type IX bonding. J Biol Chem 267: 23007–23014.

50. HannaSL, ShermanNE, KinterMT, GoldbergJB (2000) Comparison of proteins expressed by Pseudomonas aeruginosa strains representing initial and chronic isolates from a cystic fibrosis patient: an analysis by 2-D gel electrophoresis and capillary column liquid chromatography-tandem mass spectrometry. Microbiology 146: 2495–2508.

51. BonadioJ, HolbrookKA, GelinasRE, JacobJ, ByersPH (1985) Altered triple helical structure of type I procollagen in lethal perinatal osteogenesis imperfecta. J Biol Chem 260: 1734–1742.

52. KuznetsovaNV, ForlinoA, CabralWA, MariniJC, LeikinS (2004) Structure, stability and interactions of type I collagen with GLY349-CYS substitution in alpha 1(I) chain in a murine Osteogenesis Imperfecta model. Matrix Biol 23: 101–112.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa