Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastinCitation formats

  • External authors:
  • Christian E. H. Schmelzer
  • Andreas Heinz
  • Helen Troilo
  • Marion F. Marchland
  • Laurent Bidault
  • Marine Bignon
  • Tobias Hedtke
  • Alain Barret
  • Stephane Germain
  • David J. S. Hulmes
  • Laurent Muller

Standard

Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. / Schmelzer, Christian E. H.; Heinz, Andreas; Troilo, Helen; Lockhart, Michael; Jowitt, Thomas; Marchland, Marion F.; Bidault, Laurent; Bignon, Marine; Hedtke, Tobias; Barret, Alain; Mcconnell, James; Sherratt, Michael; Germain, Stephane; Hulmes, David J. S.; Baldock, Clair; Muller, Laurent.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 4, 01.04.2019, p. 5468-5481.

Research output: Contribution to journalArticlepeer-review

Harvard

Schmelzer, CEH, Heinz, A, Troilo, H, Lockhart, M, Jowitt, T, Marchland, MF, Bidault, L, Bignon, M, Hedtke, T, Barret, A, Mcconnell, J, Sherratt, M, Germain, S, Hulmes, DJS, Baldock, C & Muller, L 2019, 'Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin', The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 33, no. 4, pp. 5468-5481. https://doi.org/10.1096/fj.201801860rr

APA

Schmelzer, C. E. H., Heinz, A., Troilo, H., Lockhart, M., Jowitt, T., Marchland, M. F., Bidault, L., Bignon, M., Hedtke, T., Barret, A., Mcconnell, J., Sherratt, M., Germain, S., Hulmes, D. J. S., Baldock, C., & Muller, L. (2019). Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(4), 5468-5481. https://doi.org/10.1096/fj.201801860rr

Vancouver

Schmelzer CEH, Heinz A, Troilo H, Lockhart M, Jowitt T, Marchland MF et al. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 Apr 1;33(4):5468-5481. https://doi.org/10.1096/fj.201801860rr

Author

Schmelzer, Christian E. H. ; Heinz, Andreas ; Troilo, Helen ; Lockhart, Michael ; Jowitt, Thomas ; Marchland, Marion F. ; Bidault, Laurent ; Bignon, Marine ; Hedtke, Tobias ; Barret, Alain ; Mcconnell, James ; Sherratt, Michael ; Germain, Stephane ; Hulmes, David J. S. ; Baldock, Clair ; Muller, Laurent. / Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 4. pp. 5468-5481.

Bibtex

@article{ddec2a0ec84b40539b652225d8d00de4,
title = "Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin",
abstract = "Lysyl oxidases play a central role in extracellular matrix remodelling during development and tumour growth and fibrosis, through cross-linking of collagens and elastin. We have limited knowledge of the structure and substrate specificity of these secreted enzymes. Lysyl oxidases share a conserved C-terminal catalytic domain but differ in their N-terminal region, which is composed of four repeats of scavenger receptor cysteine-rich (SRCR) domains in LOXL2. We investigated by X-ray scattering and electron microscopy the low-resolution structure of the full-length enzyme and of a shorter form lacking the catalytic domain. Our data demonstrate that LOXL2 has a rod-like structure with a stalk composed of the SRCR domains and the catalytic domain at its tip. We detected direct interaction between LOXL2 and tropoelastin and also LOXL2-mediated deamination of tropoelastin. Using proteomics, we identified several allysines together with cross-linked tropoelastin peptides. The elastin-like material generated was resistant to trypsin proteolysis and displayed mechanical properties similar to mature elastin. Finally, we detected the codistribution of LOXL2 and elastin in the vascular wall. Altogether, these data suggest that LOXL2 could participate in elastogenesis in vivo and could be used as a means of cross linking tropoelastin in vitro for biomimetic and cell compatible tissue engineering purposes.",
keywords = "SAXS, elastin, matrix remodeling, protein structure, proteomics",
author = "Schmelzer, {Christian E. H.} and Andreas Heinz and Helen Troilo and Michael Lockhart and Thomas Jowitt and Marchland, {Marion F.} and Laurent Bidault and Marine Bignon and Tobias Hedtke and Alain Barret and James Mcconnell and Michael Sherratt and Stephane Germain and Hulmes, {David J. S.} and Clair Baldock and Laurent Muller",
note = "Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine",
year = "2019",
month = apr,
day = "1",
doi = "10.1096/fj.201801860rr",
language = "English",
volume = "33",
pages = "5468--5481",
journal = "The FASEB journal : official publication of the Federation of American Societies for Experimental Biology",
issn = "0892-6638",
publisher = "Federation of American Societies for Experimental Biology",
number = "4",

}

RIS

TY - JOUR

T1 - Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin

AU - Schmelzer, Christian E. H.

AU - Heinz, Andreas

AU - Troilo, Helen

AU - Lockhart, Michael

AU - Jowitt, Thomas

AU - Marchland, Marion F.

AU - Bidault, Laurent

AU - Bignon, Marine

AU - Hedtke, Tobias

AU - Barret, Alain

AU - Mcconnell, James

AU - Sherratt, Michael

AU - Germain, Stephane

AU - Hulmes, David J. S.

AU - Baldock, Clair

AU - Muller, Laurent

N1 - Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Lysyl oxidases play a central role in extracellular matrix remodelling during development and tumour growth and fibrosis, through cross-linking of collagens and elastin. We have limited knowledge of the structure and substrate specificity of these secreted enzymes. Lysyl oxidases share a conserved C-terminal catalytic domain but differ in their N-terminal region, which is composed of four repeats of scavenger receptor cysteine-rich (SRCR) domains in LOXL2. We investigated by X-ray scattering and electron microscopy the low-resolution structure of the full-length enzyme and of a shorter form lacking the catalytic domain. Our data demonstrate that LOXL2 has a rod-like structure with a stalk composed of the SRCR domains and the catalytic domain at its tip. We detected direct interaction between LOXL2 and tropoelastin and also LOXL2-mediated deamination of tropoelastin. Using proteomics, we identified several allysines together with cross-linked tropoelastin peptides. The elastin-like material generated was resistant to trypsin proteolysis and displayed mechanical properties similar to mature elastin. Finally, we detected the codistribution of LOXL2 and elastin in the vascular wall. Altogether, these data suggest that LOXL2 could participate in elastogenesis in vivo and could be used as a means of cross linking tropoelastin in vitro for biomimetic and cell compatible tissue engineering purposes.

AB - Lysyl oxidases play a central role in extracellular matrix remodelling during development and tumour growth and fibrosis, through cross-linking of collagens and elastin. We have limited knowledge of the structure and substrate specificity of these secreted enzymes. Lysyl oxidases share a conserved C-terminal catalytic domain but differ in their N-terminal region, which is composed of four repeats of scavenger receptor cysteine-rich (SRCR) domains in LOXL2. We investigated by X-ray scattering and electron microscopy the low-resolution structure of the full-length enzyme and of a shorter form lacking the catalytic domain. Our data demonstrate that LOXL2 has a rod-like structure with a stalk composed of the SRCR domains and the catalytic domain at its tip. We detected direct interaction between LOXL2 and tropoelastin and also LOXL2-mediated deamination of tropoelastin. Using proteomics, we identified several allysines together with cross-linked tropoelastin peptides. The elastin-like material generated was resistant to trypsin proteolysis and displayed mechanical properties similar to mature elastin. Finally, we detected the codistribution of LOXL2 and elastin in the vascular wall. Altogether, these data suggest that LOXL2 could participate in elastogenesis in vivo and could be used as a means of cross linking tropoelastin in vitro for biomimetic and cell compatible tissue engineering purposes.

KW - SAXS

KW - elastin

KW - matrix remodeling

KW - protein structure

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=85064109296&partnerID=8YFLogxK

U2 - 10.1096/fj.201801860rr

DO - 10.1096/fj.201801860rr

M3 - Article

VL - 33

SP - 5468

EP - 5481

JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology

JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology

SN - 0892-6638

IS - 4

ER -