SASDB69: E244K monomeric human Properdin (E244K Human Properdin, E244K FP)

Basic information

• Entry: Database: SASBDB / ID: SASDB69

Sample

E244K monomeric human Properdin

• E244K Human Properdin (protein), E244K FP, Homo sapiens

Function / homology

Function:

cytoplasmic side of Golgi membrane / positive regulation of opsonization / Defective B3GALTL causes PpS / O-glycosylation of TSR domain-containing proteins / Alternative complement activation / Activation of C3 and C5 / complement activation, alternative pathway / complement activation / Regulation of Complement cascade / specific granule lumen / positive regulation of immune response / tertiary granule lumen / defense response to bacterium / immune response / endoplasmic reticulum lumen / Neutrophil degranulation / extracellular space / extracellular region

Domain/homology:

: / Thrombospondin type 1 repeat / Thrombospondin type 1 domain / Thrombospondin type-1 (TSP1) repeat superfamily / Thrombospondin type-1 (TSP1) repeat profile. / Thrombospondin type 1 repeats / Thrombospondin type-1 (TSP1) repeat

Component:

Properdin

• Biological species: Homo sapiens (human)
• Citation: Journal: EMBO J / Year: 2017; Title: Functional and structural insight into properdin control of complement alternative pathway amplification.; Authors: Dennis V Pedersen / Lubka Roumenina / Rasmus K Jensen / Trine Af Gadeberg / Chiara Marinozzi / Capucine Picard / Tania Rybkine / Steffen Thiel / Uffe Bs Sørensen / Cordula Stover / Veronique Fremeaux-Bacchi / Gregers R Andersen / ; Abstract: Properdin (FP) is an essential positive regulator of the complement alternative pathway (AP) providing stabilization of the C3 and C5 convertases, but its oligomeric nature challenges structural analysis. We describe here a novel FP deficiency (E244K) caused by a single point mutation which results in a very low level of AP activity. Recombinant FP E244K is monomeric, fails to support bacteriolysis, and binds weakly to C3 products. We compare this to a monomeric unit excised from oligomeric FP, which is also dysfunctional in bacteriolysis but binds the AP proconvertase, C3 convertase, C3 products and partially stabilizes the convertase. The crystal structure of such a FP-convertase complex suggests that the major contact between FP and the AP convertase is mediated by a single FP thrombospondin repeat and a small region in C3b. Small angle X-ray scattering indicates that FP E244K is trapped in a compact conformation preventing its oligomerization. Our studies demonstrate an essential role of FP oligomerization while our monomers enable detailed structural insight paving the way for novel modulators of complement.

Contact author

• Rasmus Jensen (Aarhus University, Aarhus, Denmark)

Models

• Model #1099: ; Type: atomic / Software: CORAL / Radius of dummy atoms: 1.90 A / Chi-square value: 1.006 / P-value: 0.609000; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: E244K monomeric human Properdin / Specimen concentration: 2.70-2.70
• Buffer: Name: 10 mM HEPES 150 mM NaCl / pH: 7.2

Entity #565

Name: E244K FP / Type: protein / Description: E244K Human Properdin / Formula weight: 49.345 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P27918
Sequence:

DPVLCFTQYE ESSGKCKGLL GGGVSVEDCC LNTAFAYQKR SGGLCQPCRS PRWSLWSTWA PCSVTCSEGS QLRYRRCVGW NGQCSGKVAP GTLEWQLQAC EDQQCCPEMG GWSGWGPWEP CSVTCSKGTR TRRRACNHPA PKCGGHCPGQ AQESEACDTQ QVCPTHGAWA TWGPWTPCSA SCHGGPHEPK ETRSRKCSAP EPSQKPPGKP CPGLAYKQRR CTGLPPCPEN LYFQGVAGGW GPWGPVSPCP VTCGLGQTME QRTCNHPVPQ HGGPFCAGDA TRTHICNTAV PCPVDGEWDS WGEWSPCIRR NMKSISCQEI PGQQSRGRTC RGRKFDGHRC AGQQQDIRHC YSIQHCPLKG SWSEWSTWGL CMPPCGPNPT RARQRLCTPL LPKYPPTVSM VEGQGEKNVT FWGRPLPRCE ELQGQKLVVE EKRPCLHVPA CKDPEEEEL

Experimental information

• Beam: Instrument name: PETRA III P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: Pilatus 2M

Scan

Title: E244K monomeric human Properdin / Measurement date: Jul 27, 2016 / Storage temperature: 20 °C / Cell temperature: 20 °C / Exposure time: 0.05 sec. / Number of frames: 20 / Unit: 1/nm /

	Min	Max
Q	0.1543	2.7991

Result

Experimental MW: 50 kDa / Type of curve: single_conc

	Guinier	Guinier error
Forward scattering, I0	16659	67.36
Radius of gyration, Rg	4.13 nm	0.04

	Min	Max
Guinier point	5	59