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PDBsum entry 6rv6
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Immune system
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PDB id
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6rv6
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References listed in PDB file
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Key reference
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Title
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Structural basis for properdin oligomerization and convertase stimulation in the human complement system.
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Authors
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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.
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Ref.
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Front Immunol, 2019,
10,
2007.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Secondary reference #1
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Title
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Crystal structure of peptide-Bound neprilysin reveals key binding interactions.
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Authors
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S.Moss,
V.Subramanian,
K.R.Acharya.
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Ref.
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FEBS Lett, 2020,
594,
327-336.
[DOI no: ]
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PubMed id
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