SASDAY4: fH1015 (Factor H CCP modules 10 to 15)

Basic information

• Entry: Database: SASBDB / ID: SASDAY4

Sample

fH1015

• Factor H CCP modules 10 to 15 (protein), fH1015, 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 #87: ; Type: dummy / Software: dammif / Radius of dummy atoms: 1.90 A / Chi-square value: 0.641601; Search similar-shape structures of this assembly by Omokage search (details)
• Model #88: ; Type: dummy / Software: gasbor / Radius of dummy atoms: 1.90 A / Chi-square value: 1.0609; Search similar-shape structures of this assembly by Omokage search (details)
• Model #89: ; Type: mix / Software: bunch / Radius of dummy atoms: 1.90 A / Comment: alternative model 1 / Chi-square value: 9.229444; Search similar-shape structures of this assembly by Omokage search (details)
• Model #90: ; Type: mix / Software: bunch / Radius of dummy atoms: 1.90 A / Comment: alternative model 2 / Chi-square value: 6.170256; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: fH1015 / Sample MW: 40.9 kDa / Specimen concentration: 2.40-10.50 / Concentration method: A280
• Buffer: Name: Potassium Phosphate / Concentration: 50.00 mM / pH: 7.4

Entity #71

Name: fH1015 / Type: protein / Description: Factor H CCP modules 10 to 15 / Formula weight: 40.9 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

AGECELPKID VHLVPDRKKD QYKVGEVLKF SCKPGFTIVG PNSVQCYHFG LSPDLPICKE QVQSCGPPPE LLNGNVKEKT KEEYGHSEVV EYYCNPRFLM KGPNKIQCVD GEWTTLPVCI VEESTCGDIP ELEHGWAQLS SPPYYYGDSV EFNCSESFTM IGHRSITCIH GVWTQLPQCV AIDKLKKCKS SNLIILEEHL KNKKEFDHNS NIRYRCRGKE GWIHTVCING RWDPEVNCSM AQIQLCPPPP QIPNSHNMTT TLNYRDGEKV SVLCQENYLI QEGEEITCKD GRWQSIPLCV EKIPCSQPPQ IEHGTINSSR SSQESYAHGT KLSYTCEGGF RISEENETTC YMGKWSSPPQ CE

Experimental information

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

Scan

Title: fh1015 / 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	0.2111	4.786

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 420 /

	Min	Max
Q	0.2629	4.119
P(R) point	22	441
R	0	10.8

Result

Type of curve: merged / Standard: BSA /

	Experimental	Standard	Porod
MW	46 kDa	46 kDa	-
Volume	-	-	68 nm3

	Guinier	P(R)
Forward scattering, I0	1.62	-
Radius of gyration, Rg	3 nm	3.1 nm

	Min	Max
D	-	10.4
Guinier point	1	98