3P5C

The structure of the LDLR/PCSK9 complex reveals the receptor in an extended conformation

Summary for 3P5C

• Entry DOI: 10.2210/pdb3p5c/pdb
• Related: 3P5B
• Descriptor: Proprotein convertase subtilisin/kexin type 9, Low density lipoprotein receptor variant, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: b-propellor, receptor, convertase, hydrolase-lipid binding protein complex, hydrolase/lipid binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q8NBP7 Q8NBP7
• Total number of polymer chains: 3
• Total formula weight: 117293.73

Authors

Lo Surdo, P.,Bottomley, M.J.,Calzetta, A.,Settembre, E.C.,Cirillo, A.,Pandit, S.,Ni, Y.,Hubbard, B.,Sitlani, A.,Carfi, A. (deposition date: 2010-10-08, release date: 2011-10-26, Last modification date: 2024-11-06)

Primary citation

Lo Surdo, P.,Bottomley, M.J.,Calzetta, A.,Settembre, E.C.,Cirillo, A.,Pandit, S.,Ni, Y.G.,Hubbard, B.,Sitlani, A.,Carfi, A.
Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH.
Embo Rep., 12:1300-1305, 2011

PubMed 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.

PubMed: 22081141
DOI: 10.1038/embor.2011.205

Experimental method

X-RAY DIFFRACTION (4.2 Å)