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Review
. 2020 Apr 26;9(5):1076.
doi: 10.3390/cells9051076.

Structure and Function of Human Matrix Metalloproteinases

Helena Laronha  1   2 , Jorge Caldeira  1   2
Affiliations
Review

Structure and Function of Human Matrix Metalloproteinases

Helena Laronha et al. Cells. .

Abstract

The extracellular matrix (ECM) is a macromolecules network, in which the most abundant molecule is collagen. This protein in triple helical conformation is highly resistant to proteinases degradation, the only enzymes capable of degrading the collagen are matrix metalloproteinases (MMPs). This resistance and maintenance of collagen, and consequently of ECM, is involved in several biological processes and it must be strictly regulated by endogenous inhibitors (TIMPs). The deregulation of MMPs activity leads to development of numerous diseases. This review shows MMPs complexity.

Keywords: TIMP; collagen; matrix metalloproteinases.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the cell membrane.
Figure 2
Figure 2
Synthesis of microfibril collagen. (a) In intracellular medium, the mRNA is transcripted by ribosome, forming the pre-peptide, which is then processed in endoplasmic reticulum, forming pro-collagen. (b) In extracellular medium, the pro-collagen is processed by collagen peptidase, forming tropocollagen. For microfibril collagen formation, the tropocollagen is processed by lysil oxidase.
Figure 3
Figure 3
Collagen degradation. The enzyme with collagenolytic activity (collagenases) cleaves the triple helix at two fragments: 3/4 N-terminal and 1/4 C-terminal. Each chain (α1 and α2) has a specific cleavage sequence (# represents the cleavage site).
Figure 4
Figure 4
Active site of matrix metalloproteinase (MMP)-1. The zinc catalytic is represented by grey ball and the three histidine residues are represented by sticks.
Figure 5
Figure 5
Schematic representation of the general structure of MMP.
Figure 6
Figure 6
MMP-2 with pro-domain. (a) Surface of MMP-2, where the pro-domain is represented in orange. (b) Three-dimensional structure of MMP-2, where “bait-region” and “cysteine switch” are represented in blue.
Figure 7
Figure 7
MMP-1 catalytic domain.
Figure 8
Figure 8
MMP-1 catalytic domain, hemopexin-like domain and linker.
Figure 9
Figure 9
(a) MMP-1 hemopexin-like domain, composed to 4 β-propeller (4 β- sheets and 1 α-helix). (b) Surface of pro-MMP-2-TIMP-2 complex (pro-domain, catalytic domain and hemopexin-like domain are represented in green; TIMP-2 is represented in blue).
Figure 10
Figure 10
Schematic representation of different subgroups of S1′ pocket.
Figure 11
Figure 11
Schematic representation of MMP activation.
Figure 12
Figure 12
Catalytic mechanism.
See this image and copyright information in PMC

References

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