PMID- 31827179
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20240422
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Dec 11
TI  - Structural studies of the MMP-3 interaction with triple-helical collagen 
      introduce new roles for the enzyme in tissue remodelling.
PG  - 18785
LID - 10.1038/s41598-019-55266-9 [doi]
LID - 18785
AB  - Matrix metalloproteinase-3 (MMP-3) participates in normal extracellular matrix 
      turnover during embryonic development, organ morphogenesis and wound healing, and 
      in tissue-destruction associated with aneurysm, cancer, arthritis and heart 
      failure. Despite its inability to cleave triple-helical collagens, MMP-3 can 
      still bind to them, but the mechanism, location and role of binding are not 
      known. We used the Collagen Toolkits, libraries of triple-helical peptides that 
      embrace the entire helical domains of collagens II and III, to map MMP-3 
      interaction sites. The enzyme recognises five sites on collagen II and three 
      sites on collagen III. They share a glycine-phenylalanine-hydroxyproline/alanine 
      (GFO/A) motif that is recognised by the enzyme in a context-dependent manner. 
      Neither MMP-3 zymogen (proMMP-3) nor the individual catalytic (Cat) and hemopexin 
      (Hpx) domains of MMP-3 interact with the peptides, revealing cooperative binding 
      of both domains to the triple helix. The Toolkit binding data combined with 
      molecular modelling enabled us to deduce the putative collagen-binding mode of 
      MMP-3, where all three collagen chains make contacts with the enzyme in the 
      valley running across both Cat and Hpx domains. The observed binding pattern 
      casts light on how MMP-3 could regulate collagen turnover and compete with 
      various collagen-binding proteins regulating cell adhesion and proliferation.
FAU - Manka, Szymon W
AU  - Manka SW
AD  - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, 
      Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK. 
      s.manka@ucl.ac.uk.
AD  - MRC Prion Unit at UCL, Institute of Prion Diseases, 33 Cleveland Street, London, 
      W1W 7FF, UK. s.manka@ucl.ac.uk.
FAU - Bihan, Dominique
AU  - Bihan D
AD  - Department of Biochemistry, University of Cambridge, Cambridge, UK.
FAU - Farndale, Richard W
AU  - Farndale RW
AD  - Department of Biochemistry, University of Cambridge, Cambridge, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - RG/09/003/27122/BHF_/British Heart Foundation/United Kingdom
GR  - RG/15/4/31268/BHF_/British Heart Foundation/United Kingdom
GR  - 094470/Z/10/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191211
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Collagen/chemistry/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 1/*metabolism
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Models, Molecular
MH  - Protein Binding
MH  - Protein Folding
PMC - PMC6906530
COIS- The authors declare no competing interests.
EDAT- 2019/12/13 06:00
MHDA- 2020/11/11 06:00
PMCR- 2019/12/11
CRDT- 2019/12/13 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2019/11/14 00:00 [accepted]
PHST- 2019/12/13 06:00 [entrez]
PHST- 2019/12/13 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/12/11 00:00 [pmc-release]
AID - 10.1038/s41598-019-55266-9 [pii]
AID - 55266 [pii]
AID - 10.1038/s41598-019-55266-9 [doi]
PST - epublish
SO  - Sci Rep. 2019 Dec 11;9(1):18785. doi: 10.1038/s41598-019-55266-9.