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Updated: May 27, 2026

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH
Paola Lo Surdo1, Matthew J Bottomley, Alessandra Calzetta
1Department of Biochemistry and Molecular Biology, IRBM P. Angeletti, Via Pontina Km 30.600, Pomezia, Rome I-00040, Italy.
Abstract:
The protein PCSK9 (proprotein convertase subtilisin/kexin type 9) is a key regulator of low-density lipoprotein receptor (LDLR) levels and cardiovascular health. We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. The structure shows LDLR in a new extended conformation. The PCSK9 C-terminal domain is solvent exposed, enabling cofactor binding, whereas the catalytic domain and prodomain interact with LDLR epidermal growth factor(A) and β-propeller domains, respectively. Thus, PCSK9 seems to hold LDLR in an extended conformation and to interfere with conformational rearrangements required for LDLR recycling.
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