MMP1

Matrix metallopeptidase 1 (interstitial collagenase)

PDB rendering based on 1ayk.
Identifiers
Symbols MMP1; CLG; CLGN
External IDs OMIM120353 MGI1933846 HomoloGene20544 GeneCards: MMP1 Gene
EC number 3.4.24.7
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 4312 83995
Ensembl ENSG00000196611 ENSMUSG00000043089
UniProt P03956 Q149J4
RefSeq (mRNA) NM_001145938.1 NM_032006.3
RefSeq (protein) NP_001139410.1 NP_114395.1
Location (UCSC) Chr 11:
102.66 – 102.67 Mb
Chr 9:
7.46 – 7.48 Mb
PubMed search [1] [2]

Interstitial collagenase also known as matrix metalloproteinase-1 (MMP-1) and fibroblast collagenase is an enzyme that in humans is encoded by the MMP1 gene.[1][2][3] Human Fibroblast Collagenase (MMP-1) was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA.[4][5]

Contents

Structural Features

MMP-1, as the other members of matrix metalloproteinases family, is structurally formed by different proteic building blocks. The structural rearrangement of MMP-1 is one the simplest that can be found in MMP-1, consisting, in the active form, of a Catalytic Domain, a linker region and the Hemopexin-like Domain.[6] The primary structure of MMP-1 was first published by Goldberg, G I, et al.[5] 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 ~40Å.[7] 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.[8]

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.[8]

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 behing commonly designated as "short loop" briging 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.[9]

A specific region (183)RWTNNFREY(191) as been identified as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity.[10] 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.[11][12] 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

Proteins of the matrix metalloproteinase (MMP) family 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes a secreted enzyme which breaks down the interstitial collagens, types I, II, and III. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.[1]

In addition, mechanical force may increase the expression of MMP1 in human periodontal ligament cells.[13]

Interactions

MMP1 has been shown to interact with CD49b.[15][16]

References

  1. ^ a b EntrezGene 4312
  2. ^ Brinckerhoff, C E; Ruby, P L; Austin, S D; Fini, M E; White, H D (1987). "Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA". Journal of Clinical Investigation 79 (2): 542–6. doi:10.1172/JCI112845. PMC 424122. PMID 3027129. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=424122. 
  3. ^ Pendas, A; Santamaría, I; Alvarez, MV; Pritchard, M; López-Otín, C (1996). "Fine Physical Mapping of the Human Matrix Metalloproteinase Genes Clustered on Chromosome 11q22.3". Genomics 37 (2): 266–8. doi:10.1006/geno.1996.0557. PMID 8921407. 
  4. ^ Gross, J. (1962). "Collagenolytic Activity in Amphibian Tissues: A Tissue Culture Assay". Proceedings of the National Academy of Sciences 48 (6): 1014–22. doi:10.1073/pnas.48.6.1014. PMC 220898. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=220898. 
  5. ^ a b Goldberg, GI; Wilhelm, SM; Kronberger, A; Bauer, EA; Grant, GA; Eisen, AZ (1986). "Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein". The Journal of biological chemistry 261 (14): 6600–5. PMID 3009463. 
  6. ^ Li, J; Brick, P; O'Hare, MC; Skarzynski, T; Lloyd, LF; Curry, VA; Clark, IM; Bigg, HF et al. (1995). "Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed β-propeller". Structure 3 (6): 541–9. doi:10.1016/S0969-2126(01)00188-5. PMID 8590015. 
  7. ^ Tallant, Cynthia; Marrero, Aniebrys; Gomis-Rüth, F.Xavier (2010). "Matrix metalloproteinases: Fold and function of their catalytic domains". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1803: 20–8. doi:10.1016/j.bbamcr.2009.04.003. 
  8. ^ a b Spurlino, John C.; Smallwood, Angela M.; Carlton, Dennis D.; Banks, Tracey M.; Vavra, Karen J.; Johnson, Jeffrey S.; Cook, Ewell R.; Falvo, Joseph et al. (1994). "1.56 Å structure of mature truncated human fibroblast collagenase". Proteins: Structure, Function, and Genetics 19 (2): 98–109. doi:10.1002/prot.340190203. 
  9. ^ Maskos, Klaus; Bode, Wolfram (2003). "Structural Basis of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases". Molecular Biotechnology 25 (3): 241–66. doi:10.1385/MB:25:3:241. PMID 14668538. 
  10. ^ Chung, L.; Shimokawa, K; Dinakarpandian, D; Grams, F; Fields, GB; Nagase, H (2000). "Identification of the 183RWTNNFREY191 Region as a Critical Segment of Matrix Metalloproteinase 1 for the Expression of Collagenolytic Activity". Journal of Biological Chemistry 275 (38): 29610–7. doi:10.1074/jbc.M004039200. PMID 10871619. 
  11. ^ Bode, Wolfram; Gomis-Rüth, Franz-Xaver; Stöckler, Walter (1993). "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 Letters 331 (1–2): 134–40. doi:10.1016/0014-5793(93)80312-I. PMID 8405391. 
  12. ^ Stöcker, Walter; Grams, Frank; Reinemer, Peter; Bode, Wolfram; Baumann, Ulrich; Gomis-Rüth, Franz-Xaver; McKay, David B. (2008). "The metzincins - Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a super family of zinc-peptidases". Protein Science 4 (5): 823–40. doi:10.1002/pro.5560040502. PMC 2143131. PMID 7663339. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2143131. 
  13. ^ Huang, Sheng-Fu; Li, Yu-Hong; Ren, Yi-jin; Cao, Zheng-Guo; Long, Xing (2008). "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". European Journal of Oral Sciences 116 (4): 319–23. doi:10.1111/j.1600-0722.2008.00552.x. PMID 18705799. 
  14. ^ Reviglio, Victor E; Hakim, Melinda A; Song, Jae K; O'Brien, Terrence P (2003). "Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea". BMC Ophthalmology 3: 10. doi:10.1186/1471-2415-3-10. PMC 239861. PMID 14529574. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=239861. 
  15. ^ Stricker, T. P.; Dumin, JA; Dickeson, SK; Chung, L; Nagase, H; Parks, WC; Santoro, SA (2001). "Structural Analysis of the alpha 2 Integrin I Domain/Procollagenase-1 (Matrix Metalloproteinase-1) Interaction". Journal of Biological Chemistry 276 (31): 29375–81. doi:10.1074/jbc.M102217200. PMID 11359774. 
  16. ^ Dumin, J. A.; Dickeson, SK; Stricker, TP; Bhattacharyya-Pakrasi, M; Roby, JD; Santoro, SA; Parks, WC (2001). "Pro-collagenase-1 (Matrix Metalloproteinase-1) Binds the alpha 2beta 1 Integrin upon Release from Keratinocytes Migrating on Type I Collagen". Journal of Biological Chemistry 276 (31): 29368–74. doi:10.1074/jbc.M104179200. PMID 11359786. 

Further reading

  • Krane, SM (1995). "Is collagenase (matrix metalloproteinase-1) necessary for bone and other connective tissue remodeling?". Clinical orthopaedics and related research (313): 47–53. PMID 7641497. 
  • Massova, I; Kotra, LP; Fridman, R; Mobashery, S (1998). "Matrix metalloproteinases: Structures, evolution, and diversification". The FASEB journal 12 (12): 1075–95. PMID 9737711. 
  • Nagase, H.; Woessner Jr, JF (1999). "Matrix Metalloproteinases". Journal of Biological Chemistry 274 (31): 21491–4. doi:10.1074/jbc.274.31.21491. PMID 10419448. 
  • Okada, Y; Hashimoto, G (2001). "Degradation of extracellular matrix by matrix metalloproteinases and joint destruction". Seikagaku 73 (11): 1309–21. PMID 11831026. 
  • Seiki, Motoharu (2003). "Membrane-type 1 matrix metalloproteinase: A key enzyme for tumor invasion". Cancer Letters 194 (1): 1–11. doi:10.1016/S0304-3835(02)00699-7. PMID 12706853. 
  • Golubkov, Vladislav S.; Strongin, Alex Y. (2007). "Proteolysis-Driven Oncogenesis". Cell Cycle 6 (2): 147–50. doi:10.4161/cc.6.2.3706. PMID 17245132. 

External links