Biology:Interstitial collagenase

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Interstitial collagenase, also known as fibroblast collagenase and matrix metalloproteinase-1 (MMP-1), is an enzyme that in humans is encoded by the MMP1 gene.[1][2][3][4] The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.[2] MMP-1 was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA.[5][6] MMP-1 has an estimated molecular mass of 54 kDa.[7]

Structure

MMP-1 has an archetypal structure consisting of a pre-domain, a pro-domain, a catalytic domain, a linker region and a hemopexin-like domain.[8] The primary structure of MMP-1 was first published by Goldberg, G I, et al.[6] Two main nomenclatures for the primary structure are currently in use, the original one from which the first amino-acid starts with the signalling peptide and a second one where the first amino-acid starts counting from the prodomain (proenzyme nomenclature).

Catalytic domain

The catalytic domains of MMPs share very similar characteristics, having a general shape of oblate ellipsoid with a diameter of ~40 Å.[9] Despite the similarity of the catalytic domains of MMPs, this entry will focus only on the structural features of MMP-1 catalytic domain.

Overall structural characteristics

The catalytic domain of MMP-1 is composed of five highly twisted β-strands (sI-sV), three α-helix (hA-hC) and a total of eight loops, enclosing a total of five metal ions, three Ca2+ and two Zn2+, one of which with catalytic role.[10]

The catalytic domain (CAT) of MMP-1 starts with the F100 (non-truncated CAT) as the first amino-acid of the N-terminal loop of the CAT domain. The first published x-ray structure of the CAT domain was representative of the truncated form of this domain, where the first 7 amino-acids are not present.[10]

After the initial loop, the sequences follows to the first and longest β-sheet (sI). A second loop precedes large "amphipathic α-helix" (hA) that longitudinally spans protein site. The β-strands sII and sIII follows separated by the respective loops, loop 4 being commonly designated as "short loop" bridging sII to sIII. Following the sIII strand the sequence meets the 'S-shaped double loop' that is of primary importance for the peptide structure and catalytic activity (see further) as it extends to the cleft side "bulge", continuing to the only antiparallel β-strand sIV, which is prime importance for binding peptidic substrates or inhibitors by forming main chain hydrogen bond. Following sIV, loop Gln186-Gly192 and β-strand sV are responsible for contributing with many ligands to the several metal ions present in the protein (read further). A large open loop follows sV which has proven importance in substrate specificity within the MMPs family.[11] A specific region (183)RWTNNFREY(191) has been identified as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity.[12] On C-terminal part of the CAT Domain the hB α-helix, known as the "active-site helix" encompasses part of the "zinc-binding consensus sequence" HEXXHXXGXXH that is characteristic of the Metzincin superfamily.[13][14] The α-helix hB finishes abruptly at Gly225 where the last loop of the domain starts. This last loop contains the "specificity loop" which is the shortest in the MMPs family. The Catalytic Domain ends at Gly261 with α-helix hC.

Function

MMPs are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Specifically, MMP-1 breaks down the interstitial collagens, types I, II, and III.

Induction of matrix metalloproteinase 1 in rat corneas by ciprofloxacin, ofloxacin and levofloxacin (b,c,d) compared to artificial tears (a). Reviglio et al., 2003.

Regulation

Mechanical force may increase the expression of MMP1 in human periodontal ligament cells.[15] During cancer progression, MMP1 can be dysregulated by different mechanisms, including the activation of an insulator element located between MMP8 and MMP10 genes.[16]

Interactions

MMP1 has been shown to interact with CD49b.[17][18]

References

  1. ↑ "UniProt". https://www.uniprot.org/uniprotkb/P03956/entry#names_and_taxonomy. 
  2. ↑ 2.0 2.1 EntrezGene 4312
  3. ↑ "Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA". J. Clin. Invest. 79 (2): 542–6. February 1987. doi:10.1172/JCI112845. PMID 3027129. 
  4. ↑ "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3". Genomics 37 (2): 266–8. October 1996. doi:10.1006/geno.1996.0557. PMID 8921407. 
  5. ↑ "Collagenolytic activity in amphibian tissues: a tissue culture assay". Proc. Natl. Acad. Sci. U.S.A. 48 (6): 1014–22. June 1962. doi:10.1073/pnas.48.6.1014. PMID 13902219. Bibcode: 1962PNAS...48.1014G. 
  6. ↑ 6.0 6.1 "Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein". J. Biol. Chem. 261 (14): 6600–5. May 1986. doi:10.1016/S0021-9258(19)84605-7. PMID 3009463. 
  7. ↑ "26585-1-AP" (in en). https://www.ptglab.com/products/MMP1-Antibody-26585-1-AP.htm. 
  8. ↑ "Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed beta-propeller". Structure 3 (6): 541–9. June 1995. doi:10.1016/S0969-2126(01)00188-5. PMID 8590015. 
  9. ↑ "Matrix metalloproteinases: fold and function of their catalytic domains". Biochim. Biophys. Acta 1803 (1): 20–8. January 2010. doi:10.1016/j.bbamcr.2009.04.003. PMID 19374923. 
  10. ↑ 10.0 10.1 "1.56 A structure of mature truncated human fibroblast collagenase". Proteins 19 (2): 98–109. June 1994. doi:10.1002/prot.340190203. PMID 8090713. 
  11. ↑ "Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases". Mol. Biotechnol. 25 (3): 241–66. November 2003. doi:10.1385/MB:25:3:241. PMID 14668538. 
  12. ↑ "Identification of the (183)RWTNNFREY(191) region as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity". J. Biol. Chem. 275 (38): 29610–7. September 2000. doi:10.1074/jbc.M004039200. PMID 10871619. 
  13. ↑ "Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'". FEBS Lett. 331 (1–2): 134–40. September 1993. doi:10.1016/0014-5793(93)80312-I. PMID 8405391. 
  14. ↑ "The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases". Protein Sci. 4 (5): 823–40. May 1995. doi:10.1002/pro.5560040502. PMID 7663339. 
  15. ↑ "The effect of a single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter on force-induced MMP-1 expression in human periodontal ligament cells". Eur. J. Oral Sci. 116 (4): 319–23. August 2008. doi:10.1111/j.1600-0722.2008.00552.x. PMID 18705799. 
  16. ↑ "Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors". Molecular Cancer 22 (4): 190. November 2023. doi:10.1186/s12943-023-01906-8. PMID 38017545. 
  17. ↑ "Structural analysis of the alpha(2) integrin I domain/procollagenase-1 (matrix metalloproteinase-1) interaction". J. Biol. Chem. 276 (31): 29375–81. August 2001. doi:10.1074/jbc.M102217200. PMID 11359774. 
  18. ↑ "Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen". J. Biol. Chem. 276 (31): 29368–74. August 2001. doi:10.1074/jbc.M104179200. PMID 11359786. 

Further reading

External links

  • The MEROPS online database for peptidases and their inhibitors: M10.001
  • Overview of all the structural information available in the PDB for UniProt: P03956 (Interstitial collagenase) at the PDBe-KB.




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