Tissue inhibitor of metalloproteinases

Tissue inhibitor of metalloproteinases (TIMPs) are a family of proteins that, as their name suggests, inhibit the activity of the metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM).

Structure

TIMPs are proteins of 184-194 amino acids with a net molecular weight of 21-28kDa. They are characterized by their structure, which includes 12 cysteine residues involved in the formation of six disulfide bonds. This structure is highly conserved across the TIMP family and is essential for their function.

Function

TIMPs inhibit the activity of metalloproteinases by binding to their catalytic zinc ion. This binding is reversible and can be competed by other metalloproteinase substrates. In addition to their inhibitory role, TIMPs also have other functions, such as promotion of cell proliferation and cell differentiation, and inhibition of angiogenesis.

Types

There are four known types of TIMPs in humans: TIMP1, TIMP2, TIMP3, and TIMP4. Each of these has a unique tissue distribution and inhibition profile. For example, TIMP1 and TIMP2 are found in most tissues and inhibit all known metalloproteinases, while TIMP3 is found in the ECM and inhibits a subset of the metalloproteinases.

Clinical significance

Alterations in the balance between TIMPs and metalloproteinases can lead to a variety of diseases, such as cancer, arthritis, chronic obstructive pulmonary disease (COPD), and cardiovascular disease. For example, overexpression of TIMPs has been associated with decreased tumor growth and metastasis, while underexpression has been associated with increased tumor growth and metastasis.

See also

• Matrix metalloproteinase
• Extracellular matrix
• Protease