Faculty Opinions recommendation of The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties.

Component C3 is the central protein of the complement system. During complement activation, the thioester group in C3 is slowly hydrolysed to form C3u, then the presence of C3u enables the rapid conversion of C3 into functionally active C3b. C3u shows functional similarities to C3b. To clarify this mechanism, the self-association properties and solution structures of C3 and C3u were determined using analytical ultracentrifugation and X-ray scattering. Sedimentation coefficients identified two different dimerization events in both proteins. A fast dimerization was observed in 50 mM NaCl but not in 137 mM NaCl. Low amounts of a slow dimerization was observed for C3u and C3 in both buffers. The X-ray radius of gyration RG values were unchanged for both C3 and C3u in 137 mM NaCl, but depend on concentration in 50 mM NaCl. The C3 crystal structure gave good X-ray fits for C3 in 137 mM NaCl. By randomization of the TED (thioester-containing domain)/CUB (for complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domains in the C3b crystal structure, X-ray fits showed that the TED/CUB domains in C3u are extended and differ from the more compact arrangement of C3b. This TED/CUB conformation is intermediate between those of C3 and C3b. The greater exposure of the TED domain in C3u (which possesses the hydrolysed reactive thioester) accounts for the greater self-association of C3u in low-salt conditions. This conformational variability of the TED/CUB domains would facilitate their interactions with a broad range of antigenic surfaces. The second dimerization of C3 and C3u may correspond to a dimer observed in one of the crystal structures of C3b.

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Functional characterization of a recombinant form of the C-terminal, globular head region of the B-chain of human serum complement protein, C1q

Biochemical Journal ◽

10.1042/bj3330027 ◽

1998 ◽

Vol 333 (1) ◽

pp. 27-32 ◽

Cited By ~ 32

Author(s):

Uday KISHORE ◽

Leonara E. A. LEIGH ◽

Paul EGGLETON ◽

Peter STRONG ◽

Michael V. PERDIKOULIS ◽

...

Keyword(s):

Fusion Protein ◽

Hydrophobic Interactions ◽

Functional Characterization ◽

Gel Filtration ◽

Modular Organization ◽

Classical Pathway ◽

Complement Protein ◽

Head Region ◽

Globular Structure ◽

Globular Head

The first step in the activation of the classical pathway of the complement system by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of IgG or IgM. The globular heads of C1q are located C-terminal to the six triple-helical stalks present in the molecule; each head is considered to be composed of the C-terminal halves (3×136 residues) of one A-, one B- and one C-chain. It is not known if the C-terminal globular regions, present in each of the three types of chain, are independently folded modules (with each chain having distinct binding properties towards immunoglobulins) or whether the different binding functions of C1q are dependent upon a globular structure which relies on contributions from all three chains. As a first step towards addressing this question, we have expressed the globular head region (residues 87–226) of the C1q B-chain (ghB) as a soluble fusion protein with maltose-binding protein (MBP) in Escherichia coli. The affinity purified fusion protein, designated MBP–ghB, behaved as a dimer on gel filtration and bound preferentially to aggregated IgG rather than to IgM. It could also inhibit C1q-dependent haemolysis of both IgG- and IgM-sensitized erythrocytes. After its release from MBP, by use of Factor Xa, the free ghB exhibited a tendency to aggregate and come out of solution. Since MBP is known to be a monomeric molecule, the dimerization of the MBP–ghB fusion polypeptide is probably brought about by the ghB region, perhaps through hydrophobic interactions within the ghB region. The functional behaviour of MBP–ghB indicates that the globular regions of C1q may adopt a modular organization, i.e. each globular head of C1q may be composed of three structurally and functionally independent domains, thus retaining multivalency in the form of a heterotrimer.

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Crystal Structure of the MACPF Domain of Human Complement Protein C8α in Complex with the C8γ Subunit

Journal of Molecular Biology ◽

10.1016/j.jmb.2008.03.061 ◽

2008 ◽

Vol 379 (2) ◽

pp. 331-342 ◽

Cited By ~ 63

Author(s):

Daniel J. Slade ◽

Leslie L. Lovelace ◽

Maksymilian Chruszcz ◽

Wladek Minor ◽

Lukasz Lebioda ◽

...

Keyword(s):

Crystal Structure ◽

Human Complement ◽

Complement Protein ◽

Macpf Domain

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Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

The Journal of Immunology ◽

10.4049/jimmunol.176.5.2950 ◽

2006 ◽

Vol 176 (5) ◽

pp. 2950-2957 ◽

Cited By ~ 78

Author(s):

Fabian D. G. McGrath ◽

Mieke C. Brouwer ◽

Gérard J. Arlaud ◽

Mohamed R. Daha ◽

C. Erik Hack ◽

...

Keyword(s):

Complement Protein ◽

C Reactive Protein ◽

Head Region ◽

Reactive Protein ◽

Globular Head

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Crystal Structure of Human Complement Protein C8γ at 1.2 Å Resolution Reveals a Lipocalin Fold and a Distinct Ligand Binding Site†,‡

Biochemistry ◽

10.1021/bi025696i ◽

2002 ◽

Vol 41 (22) ◽

pp. 7030-7037 ◽

Cited By ~ 30

Author(s):

Eric Ortlund ◽

Chasta L. Parker ◽

Steven F. Schreck ◽

Steve Ginell ◽

Wladek Minor ◽

...

Keyword(s):

Crystal Structure ◽

Ligand Binding ◽

Binding Site ◽

Human Complement ◽

Ligand Binding Site ◽

Complement Protein

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Complement protein C1q binds soluble antigens of Leishmania major (SLA) via the globular head region, activates the classical pathway, and modulates macrophage immune response

Journal of King Saud University - Science ◽

10.1016/j.jksus.2021.101365 ◽

2021 ◽

Vol 33 (3) ◽

pp. 101365

Author(s):

Ahmed Al-Qahtani ◽

Mohammed N. Al-Ahdal ◽

Saad Alkahtani

Keyword(s):

Immune Response ◽

Leishmania Major ◽

Classical Pathway ◽

Complement Protein ◽

Head Region ◽

Globular Head

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Crystal Structure Determination of Glycerol-Containing Lipids from Electron Diffraction Data. Use of Analog Compounds Based upon Configurational Isomers of Cyclopentane-1, 2, 3-TRIOL

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077761 ◽

1977 ◽

Vol 35 ◽

pp. 24-25

Author(s):

Douglas L. Dorset ◽

Anthony J. Hancock

Keyword(s):

Crystal Structure ◽

Electron Diffraction ◽

Diffraction Data ◽

Structure Determination ◽

Crystal Surface ◽

Coherent Scattering ◽

Crystal Structure Determination ◽

Electron Diffraction Data ◽

Polar Group ◽

Axis Orientation

Lipids containing long polymethylene chains were among the first compounds subjected to electron diffraction structure analysis. It was only recently realized, however, that various distortions of thin lipid microcrystal plates, e.g. bends, polar group and methyl end plane disorders, etc. (1-3), restrict coherent scattering to the methylene subcell alone, particularly if undistorted molecular layers have well-defined end planes. Thus, ab initio crystal structure determination on a given single uncharacterized natural lipid using electron diffraction data can only hope to identify the subcell packing and the chain axis orientation with respect to the crystal surface. In lipids based on glycerol, for example, conformations of long chains and polar groups about the C-C bonds of this moiety still would remain unknown.One possible means of surmounting this difficulty is to investigate structural analogs of the material of interest in conjunction with the natural compound itself. Suitable analogs to the glycerol lipids are compounds based on the three configurational isomers of cyclopentane-1,2,3-triol shown in Fig. 1, in which three rotameric forms of the natural glycerol derivatives are fixed by the ring structure (4-7).

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