PDBsum entry 6rv6

Immune system

PDB id: 6rv6

Contents

Protein chains

165 a.a.

220 a.a.

Ligands

FUC-BGC ×3

NAG-NAG-FUC

MAN ×12

PDB id:

6rv6

Name:

Immune system

Title:

Structure of properdin lacking tsr3 based on anomalous data

Structure:

Properdin. Chain: a. Synonym: complement factor p. Engineered: yes. Other_details: tb-tsr1-tsr2 and additional residues from expression vector. Properdin. Chain: b. Synonym: complement factor p.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cfp, pfc. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_variant: hel293f. Expression_system_variant: hek293f

Resolution:

3.51Å R-factor: 0.265 R-free: 0.284

Authors:

D.V.Pedersen,G.R.Andersen

Key ref:

D.V.Pedersen et al. (2019). Structural Basis for Properdin Oligomerization and Convertase Stimulation in the Human Complement System. Front Immunol, 10, 2007. PubMed id: 31507604 DOI: 10.3389/fimmu.2019.02007

Date:

31-May-19 Release date: 21-Aug-19

Protein chain

P27918  (PROP_HUMAN) -  Properdin from Homo sapiens

Seq: 469 a.a.

Struc: 165 a.a.*

Protein chain

P27918  (PROP_HUMAN) -  Properdin from Homo sapiens

Seq: 469 a.a.

Struc: 220 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.3389/fimmu.2019.02007

Front Immunol 10:2007 (2019)

PubMed id: 31507604

Structural Basis for Properdin Oligomerization and Convertase Stimulation in the Human Complement System.

D.V.Pedersen, T.A.F.Gadeberg, C.Thomas, Y.Wang, N.Joram, R.K.Jensen, S.M.M.Mazarakis, M.Revel, C.El Sissy, S.V.Petersen, K.Lindorff-Larsen, S.Thiel, N.S.Laursen, V.Fremeaux-Bacchi, G.R.Andersen.

ABSTRACT

Properdin (FP) is a positive regulator of the immune system stimulating the activity of the proteolytically active C3 convertase C3bBb in the alternative pathway of the complement system. Here we present two crystal structures of FP and two structures of convertase bound FP. A structural core formed by three thrombospondin repeats (TSRs) and a TB domain harbors the convertase binding site in FP that mainly interacts with C3b. Stabilization of the interaction between the C3b C-terminus and the MIDAS bound Mg²⁺ in the Bb protease by FP TSR5 is proposed to underlie FP convertase stabilization. Intermolecular contacts between FP and the convertase subunits suggested by the structure were confirmed by binding experiments. FP is shown to inhibit C3b degradation by FI due to a direct competition for a common binding site on C3b. FP oligomers are held together by two sets of intermolecular contacts, where the first is formed by the TB domain from one FP molecule and TSR4 from another. The second and largest interface is formed by TSR1 and TSR6 from the same two FP molecules. Flexibility at four hinges between thrombospondin repeats is suggested to enable the oligomeric, polydisperse, and extended architecture of FP. Our structures rationalize the effects of mutations associated with FP deficiencies and provide a structural basis for the analysis of FP function in convertases and its possible role in pattern recognition.