SASDA25: fh1213 (Factor H CCP modules 12 to 13, fH1213)

Basic information

• Entry: Database: SASBDB / ID: SASDA25

Sample

fh1213

• Factor H CCP modules 12 to 13 (protein), fH1213, Homo sapiens

• Biological species: Homo sapiens (human)
• Citation: Journal: J Mol Biol / Year: 2010; Title: The central portion of factor H (modules 10-15) is compact and contains a structurally deviant CCP module.; Authors: Christoph Q Schmidt / Andrew P Herbert / Haydyn D T Mertens / Mara Guariento / Dinesh C Soares / Dusan Uhrin / Arthur J Rowe / Dmitri I Svergun / Paul N Barlow / ; Abstract: The first eight and the last two of 20 complement control protein (CCP) modules within complement factor H (fH) encompass binding sites for C3b and polyanionic carbohydrates. These binding sites cooperate self-surface selectively to prevent C3b amplification, thus minimising complement-mediated damage to host. Intervening fH CCPs, apparently devoid of such recognition sites, are proposed to play a structural role. One suggestion is that the generally small CCPs 10-15, connected by longer-than-average linkers, act as a flexible tether between the two functional ends of fH; another is that the long linkers induce a 180 degrees bend in the middle of fH. To test these hypotheses, we determined the NMR-derived structure of fH12-13 consisting of module 12, shown here to have an archetypal CCP structure, and module 13, which is uniquely short and features a laterally protruding helix-like insertion that contributes to a prominent electropositive patch. The unusually long fH12-13 linker is not flexible. It packs between the two CCPs that are not folded back on each other but form a shallow vee shape; analytical ultracentrifugation and X-ray scattering supported this finding. These two techniques additionally indicate that flanking modules (within fH11-14 and fH10-15) are at least as rigid and tilted relative to neighbours as are CCPs 12 and 13 with respect to one another. Tilts between successive modules are not unidirectional; their principal axes trace a zigzag path. In one of two arrangements for CCPs 10-15 that fit well with scattering data, CCP 14 is folded back onto CCP 13. In conclusion, fH10-15 forms neither a flexible tether nor a smooth bend. Rather, it is compact and has embedded within it a CCP module (CCP 13) that appears to be highly specialised given both its deviant structure and its striking surface charge distribution. A passive, purely structural role for this central portion of fH is unlikely.

Contact author

• Haydyn Mertens (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

Models

• Model #81: ; Type: atomic / Software: crysol / Chi-square value: 2.019241; Search similar-shape structures of this assembly by Omokage search (details)
• Model #82: ; Type: dummy / Software: dammif / Radius of dummy atoms: 1.90 A / Chi-square value: 2.493241; Search similar-shape structures of this assembly by Omokage search (details)
• Model #83: ; Type: dummy / Software: gasbor / Radius of dummy atoms: 1.90 A / Chi-square value: 3.0625; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: fh1213 / Sample MW: 13.6 kDa / Specimen concentration: 0.70-3.50 / Concentration method: A280
• Buffer: Name: Potassium Phosphate / Concentration: 50.00 mM / pH: 7.4

Entity #73

Name: fH1213 / Type: protein / Description: Factor H CCP modules 12 to 13 / Formula weight: 13.6 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

EAAGTCGDIP ELEHGWAQLS SPPYYYGDSV EFNCSESFTM IGHRSITCIH GVWTQLPQCV AIDKLKKCKS SNLIILEEHL KNKKEFDHNS NIRYRCRGKE GWIHTVCING RWDPEVNCS

Experimental information

• Beam: Instrument name: DORIS III X33 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron
• Detector: Name: MAR 345 Image Plate

Scan

Title: fh1213 / Measurement date: Dec 2, 2008 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 120 sec. / Number of frames: 1 / Unit: 1/nm /

	Min	Max
Q	0.3031	4.786

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 400 /

	Min	Max
Q	0.3054	3.061
P(R) point	1	400
R	0	7.1

Result

Type of curve: merged / Standard: BSA /

	Experimental	Standard	Porod
MW	19 kDa	19 kDa	-
Volume	-	-	20 nm3

	Guinier	P(R)
Forward scattering, I0	0.194	-
Radius of gyration, Rg	2 nm	2.2 nm

	Min	Max
D	-	7.1
Guinier point	1	153