Plant matrix metalloproteinase

Last updated November 09, 2023

Plant matrix metalloproteinases are metalloproteins and zinc enzymes found in plants.

Matrix Metalloproteinase

Matrix metalloproteinases (MMPs) are zinc endopeptidases, commonly called metzincins. MMP enzymes represent an ancient family of proteins with major similarities in genetic make-up that are present in a range of diverse organisms from unicellular bacteria to multicellular vertebrates and invertebrates. The superfamily is distinguished due to its motif consisting of three histidines bonded to zinc at the catalytic site. The metzincins are divided into four smaller families: seralysins, astacins, adamalysins (ADAMs), and MMPs. The MMP family is formed by twenty related zinc-dependent enzymes. They are noted for having the ability to degrade extracellular matrix proteins, such as collagens, laminin, and proteoglycans. These calcium- and zinc-dependent proteases are activated at neutral pH and twenty-three have been found present in mammalian cells. Plant MMPs show structural similarity to MMPs found in mammals, such as the presence of an auto-regulatory cysteine switch domain and a zinc-binding catalytic domain.^[1]

MMPs are synthesized primarily by connective tissues and have a large contribution to the initial events of tissue degradation. There are three major groups of the MMP family and each group has more than one distinct gene product that distinguishes them apart from one another on the immunological and biochemical criteria. Similar to that of induced fit by enzyme-substrate interactions, MMPs in the first group, called collagenases, have interstitial collagens. The second group, called gelatinases, degrade denatured collagens catalytically. The third group, called stromelysins, have the broadest proteolytic action and were originally confused as proteoglyconases. A less clearly described group of MMPs is the PUMP. Its RNA was taken from stromal cells in human breast carcinomas. Based on the PUMP sequence and functionality of carcinomas in the progression of malignancy, a new branch of the MMP family could have been discovered.^[2]

Extracellular Matrix

The most basic description of the plant extracellular matrix (ECM) is the cell wall, but it is actually the cell surface continuum that includes a variety of proteins with major roles in plant growth, development, and response. The ECM is composed of the primary and secondary cell walls, along with the intercellular gap between its neighboring cells. The ECM has a functional structure, along with aid in the regulation of turgor, which acts as a protective barrier and communicates with other cells using signaling pathways. In mammalian animals, extracellular matrix metalloproteinases (MMPs) modify the ECM to play significant roles in biological processes. The important role of MMP function in the extracellular matrix modification and subsequent mammalian development and signaling suggests that further study on the structure and function of these extracellular metalloproteinases may reveal new aspects of ECM modification in plant development.^[3]

Plant MMPs

All known MMPs have been studied in vertebrates; it is hypothesized that they are involved in remodeling connective tissue during development and healing. Current advances are being made in the field of Biochemistry, which will further analyze MMP-ECM interaction and their effects during plant development, stress induction, and xylem-phloem differences. SMEP1, soybean metalloendoproteinase 1, has been sequenced and characterized. It is noted that several unique divergences are in SMEP1 from that of the normal MMP family. For example, SMEP1 is said to have a free cysteine at position 94, a non-homologous insert from V103 to S121, a free sulfhydryl group, and the complete lack of the aspartate that is found in all of the other MMPs.^[4]

Studies of plant MMPs

Protein inhibitors of proteases, are present in plants, animals, and microorganisms. They are ubiquitous in nature and have a small molecular mass ranging from four to twenty-five kilo-Daltons. Different types of protease inhibition are directed toward a single class of protease. There are few reports on natural inhibitors of metalloproteinases. The metalloproteinase inhibitors (MPIs) can prevent unwanted proteolysis by denaturing their target proteases through non-competitive inhibition at an allosteric site. Five novel Lupinus albus MPIs were found and constitute the first reported protein inhibitors of metalloproteinases in plants and the first reported plant peptide inhibitors against a matrixin proteinase.^[5]

MtMMPL1, a Medicago truncatula nodulin gene identified by transcriptomics, is said to represent a novel and specific marker for root and nodule infection by Sinorhizobium meliloti. The possible role in the nitrogen-fixing symbiosis of a nodulin gene was investigated. The immune response of the plant to the alterations in the exopolysaccharides (EPSs) and lipopolysaccharides (LPSs) of various rhizobia led to the formation of enlarged infection threads (ITs) with thickened cell walls, which is often associated with plant defense reactions, and to the production of ineffective nodules in their plant host. Even though its precise role is classified as unknown, MTMMPL1 is noted as the first member of this biologically important protein family with a clear function in plant-microbe symbiotic associations.^[6]

At2-MMP from arabidopsis was found in leaves and roots of young arabidopsis and leaves, roots, and inflorescences of mature flowering plants showing strong increase of transcript abundance with aging. In the leaves, the MMP gene was expressed in the phloem, developing xylem elements, neighboring mesophyll cell layers, and epidermal cells. The flowers were noted as having the gene in pistils, ovules, and receptacles. It was concluded that the At2-MMP has a physiological role in mature aging tissue and the possibility of being involved in plant senescence.^[7]

The fungus Chondrostereum purpureum, the causal agent of silver leaf, was grown in liquid culture and agar, which caused it to secrete extracellular proteinases into the medium. The fluid dialysed by the activation of metal ions, which confirmed the presence of metalloproteinases. The silverleaf disease is a basidiomycete pathogenic on a wide range of host plants. The most notable host plant species include pomaceous and stone fruit species which are substantial for New Zealand’s economy. Cations, such as copper, zinc, and cobalt, are all inhibitory for the control of extract and stimulatory for EDTA-dialysed extract, which could possibly make the processes native cofactors. The amount of proteinases could be variable to the duration of the infection’s presence. Activity was found throughout the infected zone and not just the wound site; therefore, fungal growth and proteinase activity have a direct relationship. Even though zinc-binding metalloproteinases have been found to aid processes such as protein turnover and embryogenesis, it is still unclear as to the role they play in plants. To try to better understand MMPs’ role in plant tissue, the SMEP1 is cloned and analyzed using a polymerase chain reaction (PCR) and the rapid amplification of cDNA ends (RACE) reaction. It was found only to be present in mature leaves, which suggest that SEMP1 may play an important role in tissue modeling.^[8]

Related Research Articles

Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.

Gelatinases are enzymes capable of degrading gelatin through hydrolysis, playing a big role in degradation of the extracellular matrix and remodeling of tissue. Gelatinase is a type of Matrix Metalloproteinase (MMP), a family of enzymes that depend on zinc as a cofactor and can break down parts of the extracellular matrix. MMPs have multiple subgroups, including Gelatinase A (MMP-2) and Gelatinase B (MMP-9). Gelatinases are composed of a variety of EC numbers: Gelatinase A uses 3.4.24.24, and Gelatinase B uses 3.4.24.35, noting the ending overlap. The first digit, 3, is the class. Class 3 is hydrolases, or enzymes that catalyze hydrolysis reactions, or cleavage bonds with water. Next digit is sub-class 4, or proteases, which are enzymes who hydrolyze peptide bonds in proteins. The next number is the sub-subclass of 24, which classifies metalloendopeptidase- characterized by the existence of metal ions in the active site, in this case zinc, aiding the cleavage of peptide bonds. The last part of the EC number is the serial number, identifying specific enzymes within a sub-subclass. The 24 for Gelatinase A is a metalloproteinase that breaks down gelatin and collagen, while the 35 for Gelatinase B is for hydrolyzing peptide bonds.

Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extracellular matrix. In humans the MMP9 gene encodes for a signal peptide, a propeptide, a catalytic domain with inserted three repeats of fibronectin type II domain followed by a C-terminal hemopexin-like domain.

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2.

Matrix metalloproteinase-14 is an enzyme that in humans is encoded by the MMP14 gene.

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. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. MMP-1 was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA. MMP-1 has an estimated molecular mass of 54 kDa.

Stromelysin-1 also known as matrix metalloproteinase-3 (MMP-3) is an enzyme that in humans is encoded by the MMP3 gene. The MMP3 gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. MMP-3 has an estimated molecular weight of 54 kDa.

Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene family. The protein is thought to be a metastasis suppressor.

Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the MMP7 gene. The enzyme has also been known as matrin, putative metalloproteinase-1, matrix metalloproteinase pump 1, PUMP-1 proteinase, PUMP, metalloproteinase pump-1, putative metalloproteinase, MMP). Human MMP-7 has a molecular weight around 30 kDa.

Matrix metalloproteinase-26 also known as matrilysin-2 and endometase is an enzyme that in humans is encoded by the MMP26 gene.

Stromelysin-3 (SL-3) also known as matrix metalloproteinase-11 (MMP-11) is an enzyme that in humans is encoded by the MMP11 gene.

Matrix metalloproteinase-17 (MMP-17) also known as membrane-type matrix metalloproteinase 4 is an enzyme that in humans is encoded by the MMP17 gene.

Matrix metalloproteinase-25 is an enzyme that in humans is encoded by the MMP25 gene.

Matrix metalloproteinase 28 also known as epilysin is an enzyme that in humans is encoded by the MMP28 gene.

Matrix metalloproteinase-24 is an enzyme that in humans is encoded by the MMP24 gene.

Matrix metalloproteinase-20 (MMP-20) also known as enamel metalloproteinase or enamelysin is an enzyme that in humans is encoded by the MMP20 gene.

Metalloprotease inhibitors are cellular inhibitors of the Matrix metalloproteinases (MMPs). MMPs belong to a family of zinc-dependent neutral endopeptidases. These enzymes have the ability to break down connective tissue. The expression of MMPs is increased in various pathological conditions like inflammatory conditions, metabolic bone disease, to cancer invasion, metastasis and angiogenesis. Examples of diseases are periodontitis, hepatitis, glomerulonephritis, atherosclerosis, emphysema, asthma, autoimmune disorders of skin and dermal photoaging, rheumatoid arthritis, osteoarthritis, multiple sclerosis, Alzheimer's disease, chronic ulcerations, uterine involution, corneal epithelial defects, bone resorption and tumor progression and metastasis. Due to the role of MMPs in pathological conditions, inhibitors of MMPs may have therapeutic potential. Several other proteins have similar inhibitory effects, however none as effective. They might have other biological activities which have yet been fully characterised.

Matrix metallopeptidase 27 also known as MMP-27 is an enzyme which in humans is encoded by the MMP27 gene.

Pancreatic stellate cells (PaSCs) are classified as myofibroblast-like cells that are located in exocrine regions of the pancreas. PaSCs are mediated by paracrine and autocrine stimuli and share similarities with the hepatic stellate cell. Pancreatic stellate cell activation and expression of matrix molecules constitute the complex process that induces pancreatic fibrosis. Synthesis, deposition, maturation and remodelling of the fibrous connective tissue can be protective, however when persistent it impedes regular pancreatic function.

Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.

References

Notes

↑ Cao, J. & Zucker, S. (n.d.). Introduction to the MMP and TIMP families (structures, substrates) and an overview of diseases where MMPs have been incriminated. Biology and chemistry of matrix metalloproteinases (MMPs). Retrieved from http://www.abcam.com/index.html?pageconfig=resource&rid=11034
↑ Murphy, G., Murphy, G., & Reynolds, J. (1991). The origin of matrix metalloproteinases and their familial relationships. Federation of European Biochemical Societies, 289 (1), 4-7. doi : 10.1016/0014-5793(91)80895-A
↑ Flinn, B. (2008). Review: Plant extracellular matrix metalloproteinases. Functional Plant Biology, 35, 1183-1193.
↑ McGeehan, G., Burkhart, W., Anderegg, R., Becherer, J. D., Gillikin, J. W., & Graham, J. S. (1992). Sequencing and Characterization of the Soybean Leaf Metalloproteinase. Plant Physiol., 99, 1179-1183.
↑ Carrilho, D., Duarte, I., Francisco, R., Ricardo, C., & Duque-Magalhaes, M. (2009). Discovery of Novel Plant Peptides as Strong Inhibitors of Metalloproteinases. Protein and Peptide Letters, 16, 543-551.
↑ Combier, J., Vernie, T., Billy, F., Yahyaoui, F., Mathis, R., & Gamas, P. (2007). The MtMMPL1 Early Nodulin is a novel member of the matrix metalloproteinase family with a role in Medicago truncatula infection by Sinorhizobium meliloti. Plan Physiology, 144, 703-716.
↑ Golldack, D., Popova, O., & Dietz, K. (2002). Mutation of the Matrix Metalloproteinase At2-MMP Inhibits Growth and Causes Late Flowering and Early Senescence in Arabidopsis. The Journal of Biological Chemistry, 277 (7) 5541-5547.
↑ . Graham, J. S., Xiong, J., & Gillikin, J. W. (1991). Purification and Developmental Analysis of a Metalloendoproteinase from the Leaves of Glycine max. Plant Physiol., 97, 786-792

Bibliography

Cao, J. & Zucker, S. (n.d.). Introduction to the MMP and TIMP families (structures, substrates) and an overview of diseases where MMPs have been incriminated. Biology and chemistry of matrix metalloproteinases (MMPs). Retrieved from http://www.abcam.com/index.html?pageconfig=resource&rid=11034
Murphy, G., Murphy, G., & Reynolds, J. (1991). The origin of matrix metalloproteinases and their familial relationships. Federation of European Biochemical Societies, 289 (1), 4-7. doi : 10.1016/0014-5793(91)80895-A
Flinn, B. (2008). Review: Plant extracellular matrix metalloproteinases. Functional Plant Biology, 35, 1183-1193.
McGeehan, G., Burkhart, W., Anderegg, R., Becherer, J. D., Gillikin, J. W., & Graham, J. S. (1992). Sequencing and Characterization of the Soybean Leaf Metalloproteinase. Plant Physiol., 99, 1179-1183.
Carrilho, D., Duarte, I., Francisco, R., Ricardo, C., & Duque-Magalhaes, M. (2009). Discovery of Novel Plant Peptides as Strong Inhibitors of Metalloproteinases. Protein and Peptide Letters, 16, 543-551.
Combier, J., Vernie, T., Billy, F., Yahyaoui, F., Mathis, R., & Gamas, P. (2007). The MtMMPL1 Early Nodulin is a novel member of the matrix metalloproteinase family with a role in Medicago truncatula infection by Sinorhizobium meliloti. Plan Physiology, 144, 703-716.
Golldack, D., Popova, O., & Dietz, K. (2002). Mutation of the Matrix Metalloproteinase At2-MMP Inhibits Growth and Causes Late Flowering and Early Senescence in Arabidopsis. The Journal of Biological Chemistry, 277 (7) 5541-5547.
Graham, J. S., Xiong, J., & Gillikin, J. W. (1991). Purification and developmental Analysis of a Metalloendoproteinase from the Leaves of Glycine max. Plant Physiol., 97, 786-792.
Ao, C., Li, A., Elzaawely, A., & Tawata, S. (2008). MMP-13 Inhibitory Activity of Thirteen Selected Plant Species from Okinawa. International Journal of Pharmacology, 4 (3), 202-207.

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[1] Cao, J. & Zucker, S. (n.d.). Introduction to the MMP and TIMP families (structures, substrates) and an overview of diseases where MMPs have been incriminated. Biology and chemistry of matrix metalloproteinases (MMPs). Retrieved from http://www.abcam.com/index.html?pageconfig=resource&rid=11034

[2] Murphy, G., Murphy, G., & Reynolds, J. (1991). The origin of matrix metalloproteinases and their familial relationships. Federation of European Biochemical Societies, 289 (1), 4-7. doi : 10.1016/0014-5793(91)80895-A

[3] Flinn, B. (2008). Review: Plant extracellular matrix metalloproteinases. Functional Plant Biology, 35, 1183-1193.

[4] McGeehan, G., Burkhart, W., Anderegg, R., Becherer, J. D., Gillikin, J. W., & Graham, J. S. (1992). Sequencing and Characterization of the Soybean Leaf Metalloproteinase. Plant Physiol., 99, 1179-1183.

[5] Carrilho, D., Duarte, I., Francisco, R., Ricardo, C., & Duque-Magalhaes, M. (2009). Discovery of Novel Plant Peptides as Strong Inhibitors of Metalloproteinases. Protein and Peptide Letters, 16, 543-551.

[6] Combier, J., Vernie, T., Billy, F., Yahyaoui, F., Mathis, R., & Gamas, P. (2007). The MtMMPL1 Early Nodulin is a novel member of the matrix metalloproteinase family with a role in Medicago truncatula infection by Sinorhizobium meliloti. Plan Physiology, 144, 703-716.

[7] Golldack, D., Popova, O., & Dietz, K. (2002). Mutation of the Matrix Metalloproteinase At2-MMP Inhibits Growth and Causes Late Flowering and Early Senescence in Arabidopsis. The Journal of Biological Chemistry, 277 (7) 5541-5547.

[8] . Graham, J. S., Xiong, J., & Gillikin, J. W. (1991). Purification and Developmental Analysis of a Metalloendoproteinase from the Leaves of Glycine max. Plant Physiol., 97, 786-792

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