The serpins: nature's molecular mousetraps.
A special family of inhibitors, known as the serpins, has evolved an extraordinary mechanism to enable the control of the proteolytic pathways essential to life. The serpins undergo a profound change in conformation to entrap their target protease in an irreversible complex. The solving of the structure of this complex now completes a video depiction of the changes involved. The serpin, just like a mousetrap, is seen to change with a spring-like movement from an initial metastable state to a final hyperstable form. The structure shows how this conformational shift not only inhibits the protease but also destroys it. A bonus from these structural insights is the realisation that a number of diseases, as diverse as thrombosis, cirrhosis and dementia, all share a common mechanism arising from similar mutations of different serpins.
Huntington
J A
JA
University of Cambridge, Department of Haematology, Wellcome Trust Centre for Molecular Mechanisms in Disease, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK.
Carrell
R W
RW
D000818:Animals; D003704:Dementia / Q000201:enzymology / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015843:Serpins / Q000235:genetics* / Q000502:physiology; D013927:Thrombosis / Q000201:enzymology / Q000235:genetics*
D015843:Serpins