PDBsum entry 3p5b

Hydrolase/lipid binding protein

PDB id: 3p5b

Contents

Protein chains

92 a.a.

493 a.a.

394 a.a.

Metals

_CA ×3

PDB id:

3p5b

Name:

Hydrolase/lipid binding protein

Title:

The structure of the ldlr/pcsk9 complex reveals the receptor in an extended conformation

Structure:

Proprotein convertase subtilisin/kexin type 9. Chain: p. Synonym: neural apoptosis-regulated convertase 1, narc-1, proprotein convertase 9, pc9, subtilisin/kexin-like protease pc9. Engineered: yes. Proprotein convertase subtilisin/kexin type 9. Chain: a. Synonym: neural apoptosis-regulated convertase 1, narc-1, proprotein convertase 9, pc9, subtilisin/kexin-like protease pc9.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: narc1, pcsk9, psec0052. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293. Gene: ldlr, narc1, pcsk9, psec0052. Expression_system_cell_line: hek293

Resolution:

3.30Å R-factor: 0.271 R-free: 0.298

Authors:

P.Lo Surdo,M.J.Bottomley,A.Calzetta,E.C.Settembre,A.Cirillo,S.Pandit, Y.Ni,B.Hubbard,A.Sitlani,A.Carfi

Key ref:

P.Lo Surdo et al. (2011). Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. Embo Rep, 12, 1300-1305. PubMed id: 22081141

Date:

08-Oct-10 Release date: 26-Oct-11

Protein chain

Q8NBP7  (PCSK9_HUMAN) -  Proprotein convertase subtilisin/kexin type 9 from Homo sapiens

Seq: 692 a.a.

Struc: 92 a.a.

Protein chain

Q8NBP7  (PCSK9_HUMAN) -  Proprotein convertase subtilisin/kexin type 9 from Homo sapiens

Seq: 692 a.a.

Struc: 493 a.a.*

Protein chain

P01130  (LDLR_HUMAN) -  Low-density lipoprotein receptor from Homo sapiens

Seq: 860 a.a.

Struc: 394 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains P, A: E.C.3.4.21.- - ?????

Embo Rep 12:1300-1305 (2011)

PubMed id: 22081141

Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH.

P.Lo Surdo, M.J.Bottomley, A.Calzetta, E.C.Settembre, A.Cirillo, S.Pandit, Y.G.Ni, B.Hubbard, A.Sitlani, A.Carfí.

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.