Zinc metallopeptidase STE24 (ZMPSTE24)

Zinc metallopeptidase STE24 (ZMPSTE24) is an integral membrane zinc-dependent metalloprotease critical for the post-translational maturation of lamin A, a major structural component of the nuclear envelope. ZMPSTE24 cleaves farnesylated prelamin A at defined sites on the nuclear envelope and endoplasmic reticulum, enabling the generation of mature lamin A, which is essential for proper nuclear architecture and gene regulation[1][3][6]. The protein also acts in ER protein quality control by removing aberrant, misfolded secretory protein fragments from translocons and serves as an innate antiviral restriction factor, helping block entry and fusion of a wide range of enveloped viruses, including coronaviruses, influenza, and more[3][5]. Disease-associated mutations or drug-induced inhibition of ZMPSTE24 lead to accumulation of toxic prelamin A, precipitating progeroid syndromes (e.g., Hutchinson-Gilford progeria syndrome), lipodystrophy, restrictive dermopathy, and increased susceptibility to viral infections[1][3][5]. The unique structure of ZMPSTE24 features a seven-transmembrane barrel-like architecture with a catalytic HEXXH motif and a central chamber where substrate cleavage occurs[2][4].

Other names

CAAX prenyl protease 1 homologFACE1STE24FACE-1Ste24pFarnesylated proteins-converting enzyme 1Prenyl protein-specific endoprotease 1Zinc metalloproteinase Ste24 homologHGPSPRO1Restrictive dermopathy 1 proteinRSDM1

Competitive inhibition of enzymatic activity by HIV protease inhibitors