Structure of the nuclear membrane zinc metalloprotease ZMPSTE24

Growing old too soon

Enzymes are involved in ageing

Enzymes that are inactive, or not active enough, are among many contributors to human ageing. Progeria is a very rare exaggerated form of ageing. It is seen in children with inadequate supplies of lamin, a fibrous protein that is vital for maintaining the structure of the cell nucleus. Patients typically suffer hair loss, joint problems and heart disease, and usually die in their mid-teens.

A major cause of progeria is a defect in a protease that completes the production of lamin from its precursor, prolamin. The protease, ZMPSTE24, is a complex transmembrane protein.

In 2013 a team of X-ray crystallographers solved its 3D structure, explaining how several mutations disable the enzyme and bring on the symptoms of one type of progeria. Understanding more about this unusual protein structure may eventually help in the development of treatment for progeria and also explain the more gradual deterioration seen in normal ageing.

Lead image:

Structure of ZMPSTE24.

Structural Genomics Consortium

About this resource

This resource was first published in ‘Proteins’ in January 2014.

Topics:
Cell biology, Biotechnology and engineering
Issue:
Proteins
Education levels:
16–19, Continuing professional development