The three-dimensional structure of antibodies

Marquart, Markus; Deisenhofer, Johann

doi:10.1016/0167-5699(82)90107-4

Cited by 72 publications

(13 citation statements)

References 35 publications

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“…This algorithm always converges, but is not guaranteed to minimize Term 1. For classification in three subclasses, we ran the algorithm many times with different initial centers and in most cases it converged to the following solution (which was the minimum among all the solutions we obtained): Class I: 192 hexamers centered around hexamer 157-162 of 3RP2a (rat mast cell protease, chain a [31]); Class II: 277 hexamers around hexamer 19-24 of 1FB4h (immunoglobulin fab, chain h [32]); and Class III: 70 hexamers around hexamer 161-166 of 2SGA (Proteinase A [33]). Figure 3 shows a superposition of 30 hexamers from each of the three classes mentioned above, which shows that the classes are structurally homogeneous and quite distinct from each other.…”

Section: Short Structural Motifsmentioning

confidence: 99%

The importance of short structural motifs in protein structure analysis

Unger

Sussman

1993

J Computer-Aided Mol Des

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Proteins tend to use recurrent structural motifs on all levels of organization. In this paper we first survey the topics of recurrent motifs on the local secondary structure level and on the global fold level. Then, we focus on the intermediate level which we call the short structural motifs. We were able to identify a set of structural building blocks that are very common in protein structure. We suggest that these building blocks can be used as an important link between the primary sequence and the tertiary structure. In this framework, we present our latest results on the structural variability of the extended strand motifs. We show that extended strands can be divided into three distinct structural classes, each with its own sequence specificity. Other approaches to the study of short structural motifs are reviewed.

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Section: Short Structural Motifsmentioning

confidence: 99%

The importance of short structural motifs in protein structure analysis

Unger

Sussman

1993

J Computer-Aided Mol Des

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“…In another set of experiments the interactions between the different antibody chains were characterized by measuring the dissociation constants of light chain and heavy chain and their fragments [9]. Furthermore, the structure of several Fab fragments and one intact antibody were solved by crystallography [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Folding of the Fab fragment within the intact antibody

Lilie

1997

FEBS Letters

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At present it is not clear to which extent the Fab fragment and the Fc part of an antibody interact in the intact imiminoglobulin structure. To determine such potential interactions the unfolding and refolding of an isolated Fab fragment and the respective antibody MAK 33 (K/IgGl) are compared. It could be shown that the proline independent renaturation kinetics of both an unfolding intermediate and the fully denatured form of both proteins are identical. Upon denaturation, the loss of antigen binding activity occurs with the same rate for both the Fab fragment and the intact antibody. However, the complete structural unfolding of the Fab part of the antibody is significantly slower than that of the isolated Fab fragment. These kinetic data suggest that the structure of the Fab fragment within the intact antibody is stabilized by interactions, presumably with the Fc part, missing in the isolated Fab.

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“…Yet protein A, which binds to Fc but does not interfere with complement binding (28), inhibited the interactions of over one-half of our mIgMRF with the substrate IgG. The crystal structure of the complex between fragment B of protein A and Fc fragments indicates that protein A binds at the CH2-CH3 junction (28,56,57). Thus, the antigenic sites for 12 of the 23 mIgMRF that were strongly inhibited by protein A could be placed at or very near the CH2-CH3 junction.…”

Section: Discussionmentioning

confidence: 91%

Monoclonal IgM rheumatoid factors derived from arthritic MRL/Mp-lpr/lpr mice.

Theofilopoulos¹,

Balderas²,

Hang³

et al. 1983

The Journal of Experimental Medicine

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MRL/lpr/lpr (MRL/l) mice develop a lupus-like syndrome and a disease histologically and serologically similar to human rheumatoid arthritis. Their sera contain polyclonal IgM rheumatoid factors (RF) reactive with all murine IgG subclasses (frequently strongest with IgG2a) and several heterologous IgG. To examine the repertoire and epitopic specificities of these RF, we fused splenocytes from 3.5-mo-old seropositive MRL/l mice with appropriate myeloma partners and derived 1,723 hybridomas of which 23 secreted IgMRF. These monoclonal IgMRF bound to murine IgG only, not to other murine isotypes. Eight murine IgG subclass-specific clonotypes were identified. Most clones reacted with either multiple IgG subclasses or with IgG2a alone. A few clones reacted solely with IgG2b but none reacted exclusively with IgG1 or IgG3. Monoclonal IgMRF with exclusively anti-IgG2a activity exhibited allotypic specificity, reacting, with few exceptions, with a, c, and e, but not b, d, or j IgG2a allotypes. Four clonotypes could be distinguished by cross-reactivity with IgG from species other than mice. Monoclonals possessing activity against several murine subclasses cross-reacted extensively with heterologous IgG, including all human IgG subclasses without allotypic restrictions. Monoclonal IgMRF specific for murine IgG2a or 2b did not cross-react with heterologous IgG. Based on the absence of cross-reactions by IgG2a-specific monoclonal autoantibodies, certain peptides of the IgG CH2 and CH3 domains appear to generate the antigenic determinants of the anti-IgG2a RF in MRL/l mice. All of the monoclonal RF bound to Fc and, with one exception, not to Fab fragments of murine IgG. Binding of the monoclonal RF to substrate IgG was not inhibited by Clq, thus excluding the Clq-binding site at the CH2 domain as one of the responsible epitopes in the induction of MRL/l RF. mIgMRF could be categorized as strongly, weakly, or noninhibitable by protein A, which interacts with IgG molecules at or near the CH2-CH3 junction. Inhibition appears to be caused by conformational changes and/or steric shielding of certain IgG areas distant from this junction and not by identical binding sites between protein A and RF. Certain of the mIgMRF that were weakly or not at all inhibitable by protein A were found to cross-react equally well with human Fc (CH2-CH3 domains) and pFc' (CH3 domain) fragments, indicating that the binding site for these monoclonals is at the CH3 domain. Monoclonal RF were devoid of anti-double-strand DNA, anticollagen, or antipeptidoglycan pentapeptide cross-reactivity, but one of the monoclonals cross-reacted with histones, four with single-strand DNA, and one with both histones and single-strand DNA.

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The three-dimensional structure of antibodies

Cited by 72 publications

References 35 publications

The importance of short structural motifs in protein structure analysis

The importance of short structural motifs in protein structure analysis

Folding of the Fab fragment within the intact antibody

Monoclonal IgM rheumatoid factors derived from arthritic MRL/Mp-lpr/lpr mice.

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