Bioisis

"Allosteric inhibition of C3b complement function by Efb staphylococcal immune evasion protein"

Experimental SAS Curve

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Experimental Mass

179,000 Da

Experimental Details for BID:  C3BSAP
Experiment ID: 104
Collected at: ALS BL 12.3.1
Contributors: Weinkam, P ,  Schneidman-duhovny, D ,  Webb, B ,  Tainer, J ,  Hammel, M ,  Sali, A
SAXS profile of C3b complement and C3b-Efb. Here we demonstrate that the extracellular fibrinogenbinding protein (Efb) from S. aureus acts as an allosteric inhibitor by inducing conformational changes in complement fragment C3b that propagate across several domains and influence functional regions far distant from the Efb binding site. Most notably, the inhibitor impaired the interaction of C3b with complement factor B and, consequently, formation of the active C3 convertase.
Solution state of complement fragment C3b in the complex with extracellular fibrinogenbinding protein (Efb) from S. aureus. C3b alone or an equimolar C3b/Efb-C complex (0.5–1.2 mg/mL) measured by SAXS for both short (0.5 s) and long time exposure (5 s).

Electron Pair Distribution

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       Dmax → 176 Å


Guinier Plot

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     Guinier Rg → 46.74 Å

Real Space Rg → 48.16 Å

The Guinier plot is used to estimate the radius of gyration, Rg, which is taken from the slope of a line observed at low scattering angles (typically in the range where q* Rg < 1.3). This should be in reasonable agreement with the real space Rg.


Kratky Plot

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The Kratky plot can be used to visually assess the degree of "unfoldedness" of a protein or RNA sample. The plot of a well-behaved folded protein approaches the baseline at high q values creating a parabolic shape.


PDB Model fit to SAXS Data

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The red line is the calculated SAXS profile from a PDB model scaled to the experimental SAXS curve (cyan). The two curves agree with a Chi2 of 0.1.


Additional Experimental Details
Title

Allosteric inhibition of C3b complement function by Efb staphylococcal immune evasion protein

Description

SAXS profile of C3b complement and C3b-Efb. Here we demonstrate that the extracellular fibrinogenbinding protein (Efb) from S. aureus acts as an allosteric inhibitor by inducing conformational changes in complement fragment C3b that propagate across several domains and influence functional regions far distant from the Efb binding site. Most notably, the inhibitor impaired the interaction of C3b with complement factor B and, consequently, formation of the active C3 convertase.

Publication

Proceedings of the National Academy of Sciences of the United States of America, Vol. 107(41), 17621-17626

Contributors

Weinkam, P ,  Schneidman-duhovny, D ,  Webb, B ,  Tainer, J ,  Hammel, M ,  Sali, A

Genomics and Proteomics

The experiment is composed of a single gene/ORF

Abbreviated name: C3b

Annotation: complement C3b fragment

SPMYSIITPN ILRLESEETM VLEAHDAQGD VPVTVTVHDF PGKKLVLSSE KTVLTPATNH MGNVTFTIPA NREFKSEKGR NKFVTVQATF GTQVVEKVVL VSLQSGYLFI QTDKTIYTPG STVLYRIFTV NHKLLPVGRT VMVNIENPEG IPVKQDSLSS QNQLGVLPLS WDIPELVNMG QWKIRAYYEN SPQQVFSTEF EVKEYVLPSF EVIVEPTEKF YYIYNEKGLE VTITARFLYG KKVEGTAFVI FGIQDGEQRI SLPESLKRIP IEDGSGEVVL SRKVLLDGVR AEDLVGKSLY VSATVILHSG SDMVQAERSG IPIVTSPYQI HFTKTPKYFK PGMPFDLMVF VTNPDGSPAY RVPVAVQGED TVQSLTQGDG VAKLSINTHP SQKPLSITVR TKKQELSEAE QATRTMQALP YSTVGNSNNY LHLSVLRTEL RPGETLNVNF LLRMDRAHEA KIRYYTYLIM NKGRLLKAGR QVREPGQDLV VLPLSITTDF IPSFRLVAYY TLIGASGQRE VVADSVWVDV KDSCVGSLVV KSGQSEDRQP VPGQQMTLKI EGDHGARVVL VAVDKGVFVL NKKNKLTQSK IWDVVEKADI GCTPGSGKDY AGVFSDAGLT FTSSSGQQTA QRAELQCPQD EDIIAEENIV SRSEFPESWL WNVEDLKEPP KNGISTKLMN IFLKDSITTW EILAVSMSDK KGICVADPFE VTVMQDFFID LRLPYSVVRN EQVEIRAVLY NYRQNQELKV RVELLHNPAF CSLATTKRRH QQTVTIPPKS SLSVPYVIVP LKTGLQEVEV KAAVYHHFIS DGVRKSLKVV PEGIRMNKTV AVRTLDPERL GREGVQKEDI PPADLSDQVP DTESETRILL QGTPVAQMTE DAVDAERLKH LIVTPSGCGE ENMIGMTPTV IAVHYLDETE QWEKFGLEKR QGALELIKKG YTQQLAFRQP SSAFAAFVKR APSTWLTAYV VKVFSLAVNL IAIDSQVLCG AVKWLILEKQ KPDGVFQEDA PVIHQEMIGG LRNNNEKDMA LTAFVLISLQ EAKDICEEQV NSLPGSITKA GDFLEANYMN LQRSYTVAIA GYALAQMGRL KGPLLNKFLT TAKDKNRWED PGKQLYNVEA TSYALLALLQ LKDFDFVPPV VRWLNEQRYY GGGYGSTQAT FMVFQALAQY QKDAPDHQEL NLDVSLQLPS RSSKITHRIH WESASLLRSE ETKENEGFTV TAEGKGQGTL SVVTMYHAKA KDQLTCNKFD LKVTIKPAPE TEKRPQDAKN TMILEICTRY RGDQDATMSI LDISMMTGFA PDTDDLKQLA NGVDRYISKY ELDKAFSDRN TLIIYLDKVS HSEDDCLAFK VHQYFNVELI QPGAVKVYAY YNLEESCTRF YHPEKEDGKL NKLCRDELCR CAEENCFIQK DKVTLEERLD KACEPGVDYV YKTRLVKVQL SNDFDEYIMA IEQTIKSGSD EVQVGQQRTF ISPIKCREAL KLEEKKHYLM WGLSSDFWGE KPNLSYIIGK DTWVEHWPEE DECQDEENQK QCQDLGAFTE SMVVFGCPN
categoryamino acid composition(%)
HydrophobicI(5.2) V(9.2) L(9.2) M(2.1) A(5.8) G(5.9) P(4.9)
AromaticF(3.7) W(1.1) Y(3.6)
HydrophilicR(4.3) K(6.8) E(7.6) D(5.6) Q(5.5) N(3.7) H(1.7) S(6.5) T(6.5) C(1.4)