Conformational changes in C1q upon binding to IgG oligomers

Vandenberg, Robert J.; Easterbrook‐Smith, Simon B.

doi:10.1016/0014-5793(86)81504-6

Cited by 6 publications

(6 citation statements)

References 17 publications

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“…It has previously been shown that C1q changes conformation upon binding to aggregated Igs [4, 55]. We have found that this conformational change permits specific interaction with calreticulin, and we propose that a similar conformational change occurs when C1q is immobilized on the polystyrene surface of ELISA plates or is heat treated for a short period of time.…”

Section: Discussionmentioning

confidence: 61%

“…C1q binds to altered conformations of Ig, immunecomplexes, and aggregated Igs, for example, bound to bacterial surfaces [54]. We hypothesized that an altered conformation of C1q, reported to be induced by binding to IgG or IgM [4,55], would allow calreticulin to recognize C1q, and this was confirmed by several experiments (Fig. 1A).…”

Section: Binding To Immunoglobulins Induces a Conformational Change Imentioning

confidence: 55%

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Interaction of C1q with the Receptor Calreticulin Requires a Conformational Change in C1q

2004

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The interaction between C1q and the chaperone calreticulin was studied under various conditions. When both proteins were present in equal amounts in solution, no interaction could be demonstrated. However, C1q immobilized on a hydrophobic surface, exposed to heat-treatment or bound to immunoglobulins (Igs) showed a strong, rapid and specific binding of calreticulin. The interaction appeared to be a two-step process, and the initial phase of interaction was sensitive to high concentrations of salt but not to a physiological salt concentration. The following strong binding was insensitive to salt and extremes of pH but sensitive to strongly denaturing agents (urea and guanidine). The sensitivity to salt during the initial phase of interaction was practically identical to that observed when calreticulin was bound to type V collagen. Binding between C1q and calreticulin could be inhibited by serum amyloid P component and by proteinase K-digested ovalbumin, and the binding of calreticulin to proteinase K-digested ovalbumin was shown to be inhibited by C1q. The data indicate that C1q binds stably to the peptide-binding site of calreticulin and that the initial binding of calreticulin to C1q involves the collagen-like domain of the C1q molecule. In conclusion, our results suggest calreticulin as a potential receptor for an altered conformation of C1q as occurs during binding to Igs. Thus, the chaperone and protein-scavenging function of calreticulin may extend from the endoplasmic reticulum to the topologically equivalent cell surface, where it may contribute to the elimination of immune complexes and apoptotic cells.

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Section: Discussionmentioning

confidence: 61%

Section: Binding To Immunoglobulins Induces a Conformational Change Imentioning

confidence: 55%

Interaction of C1q with the Receptor Calreticulin Requires a Conformational Change in C1q

2004

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“…Hansen, N. Thielens, G. Arlaud, L. Kongerslev, S. Thiel, P. Højrup, G. Houen, unpublished observations). C1q has previously been shown to undergo a conformational change upon binding to a solid surface or aggregated IgG thus allowing interaction with calreticulin [19, 20]. Similarly, upon binding to the solid phase of the microtitre plates, CD40L changes conformation, thus allowing interaction with calreticulin, which itself changes conformation upon binding as evidenced by the binding characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Calreticulin is an endoplasmic reticulum (ER) chaperone, which has also been reported to be present at the cell surface in complex with various receptors and to function as a co-receptor for these, thereby mediating internalization of apoptotic cells, pathogens and aggregated immunoglobulins bound to collectins or C1q [1,[9][10][11][12][13][14][15][16][17][18]. Notably, the interaction between calreticulin and C1q has been found to depend on structural changes in C1q, such as it occurs upon the binding of C1q to a surface or to aggregated immunoglobulins [19,20].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Calreticulin with CD40 Ligand, TRAIL and Fas Ligand

et al. 2007

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The molecular chaperone calreticulin has been shown to bind C1q and mannan‐binding lectin (MBL), which are constituents of the innate immune defence system. C1q and MBL do not share a large sequence identity but have a similar overall molecular architecture: an N‐terminal triple‐helical collagen‐like domain and a C‐terminal globular domain with ligand‐binding properties. C1q is a hetero‐trimer, while MBL is a homo‐trimer, but due to the presence of N‐terminal cysteines they both form higher order oligomers of trimers, which are the mature functional molecules. The same molecular architecture is utilized by many other functionally diverse molecules and in this work the interaction of calreticulin with C1q and structurally similar molecules was investigated. In addition to C1q and MBL, CD40 ligand (CD40L), tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and Fas ligand (FasL) were found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor‐α (TNF‐α), CD30L, surfactant protein‐A and ‐D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same characteristics as calreticulin’s interaction with C1q and MBL: a time‐dependent saturable binding to immobilized protein, which was initially sensitive to salt but gradually developed into a salt‐insensitive interaction. Thus, the interaction requires a structural change in the interaction partner and leads to a conformational change in calreticulin itself. The implications of these results are that calreticulin may function as a general response modifier for a whole group of immunologically important proteins.

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“…This produces a curve similar to a DSC thermogram, which can be used to evaluate excipients for their ability to modulate thermal stability [79]. ANS fluorescence has been used for other related purposes, such as the investigation of protein interactions with ligands [80] and toxins [48], or detecting conformational changes related to binding sites [49].…”

Section: Techniques To Analyse Protein 3° Structurementioning

confidence: 99%

Analytical techniques for the evaluation of liquid protein therapeutics

Tatford

Gomme

Bertolini

2004

Biotech and App Biochem

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A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. Analytical techniques are required to study the propensity of solutions to form aggregates and particles and to allow the investigation of the effect of conditions encountered during manufacture and storage. A key challenge is to utilize appropriate specific and sensitive techniques to allow the early detection of initial aggregation events, thereby avoiding the need to resort to extended stability trials. The present review evaluates a range of techniques for the detection of changes in protein conformation and the formation of aggregates and particles. It is hoped that the availability of this information will encourage and facilitate studies to resolve stability issues associated with protein therapeutics.

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Conformational changes in C1q upon binding to IgG oligomers

Cited by 6 publications

References 17 publications

Interaction of C1q with the Receptor Calreticulin Requires a Conformational Change in C1q

Interaction of C1q with the Receptor Calreticulin Requires a Conformational Change in C1q

Interaction of Calreticulin with CD40 Ligand, TRAIL and Fas Ligand

Analytical techniques for the evaluation of liquid protein therapeutics

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