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Spatial structure of immunoglobulin molecules

Die räumliche Struktur der Immunglobulin-Moleküle

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Zusammenfassung

Immunglobulin Moleküle der Klasse G (Antikörper-Moleküle) bestehen aus zwei schweren Ketten (50 000 dalton Molekulargewicht) und zwei leichten Ketten (25 000 dalton Molekulargewicht). Ihre Gestalt ist Y-förmig, wobei die Arme von je einer leichten Kette und der N-terminalen Hälfte einer schweren Kette in enger Assoziation gebildet werden. Der Stamm wird von den C-terminalen Hälften der schweren Ketten aufgebaut.

Die schweren und die leichten Ketten sind in globuläre Domänen mit einem Molekulargewicht von 12 000 dalton gefaltet. Die schweren Ketten bestehen aus vier, die leichten Ketten aus zwei Domänen. Diiese Domänen zeigen eine ähnliche Grundstruktur aus zwei β-Faltblättern, aber erhebliche Unterschiede im Detail.

Die N-terminalen, variablen Domänen der schweren und leichten Ketten, spezifisch die hypervariablen Polypeptidesegmente der Domänen, die an den Spitzen des Y liegen, bauen die Antigen- und Hapten-Bindungsstelle auf. Die Art der Aminosäuren in den hypervariablen Schleifen bestimmt die Form und die Spezifität des Antikörpers. Alle Domänen mit Ausnahme der CH2 Domäne der schweren Kette aggregieren eng lateral. Die CH2 Domäne hat Kohlehydrat gebunden, das die laterale Assoziation verhindert.

Longitudinale Wechselwirkungen zwischen den Domänen sind locker und erlauben Flexibilität in der relativen Anordnung der Domänen. Diese Flexibilität ist wahrscheinlich für die Funktion der Antikörper von Bedeutung.

Arm (Fab) und Stamm (Fc) Teile sind durch ein Scharnierpeptide verbunden, das zwei parallelen Polyproline Helizes enthält.

Antigenbindung initialisiert die Effektorfunktionen der Antikörper. Antigen bindet an die Spitzen des Y-förmigen Moleküls, die Effektorfunktionen sind im Stammteil lokalisiert. Es ist eine offene Frage, ob Konformationsänderungen im Antikörpermolekül bei der Initialisierung eine Rolle spielen.

Summary

Immunoglobulin molecules of the class G (antibody molecules) consist of two heavy chains (50,000 dalton molecular weight) and two light chains (25,000 dalton). The overall shape is a Y with the arms formed by the light chains and the N-terminal half of the heavy chains in tight association. The stem is formed by the C-terminal halfs of the heavy chains.

The heavy and the light chains fold into globular domains of molecular weights of 12,000 dalton. There are four domains of the heavy chain and two of the light chain. All these domains show a similar fold, consisting of two β-sheets but display considerable differences in detail.

The N-terminal variable domains of heavy and light chains and specifically the hypervariable polypeptide segments of the domains, located at the tips of the Y, constitute the antigen and hapten binding site. The nature of the amino acid residues of the hypervariable loops determines the shape and the specificity of the antibody.

All domains pair tightly laterally, except the CH2 domains of the heavy chain. This domain has carbohydrate bound which prevents lateral association.

Longitudinal interaction between the domains is loose and allows flexibility in the arrangement. Flexibility is probably of significance for antibody function.

Arm (Fab) and stem (Fc) parts are linked by the hinge peptide which contains a segment with a unique conformation of two parallel poly-proline helices.

Antigen binding triggers effector functions of antibodies. Antigen binding is at the tips of the Y-shaped antibody, but effector functions are displayed by the stem part. It is an open question whether conformational changes of the antibody molecule play a significant role in the trigger mechanism.

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  1. Max-Planck-Institut für Biochemie, Martinsried

    R. Huber

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Huber, R. Spatial structure of immunoglobulin molecules. Klin Wochenschr 58, 1217–1231 (1980). https://doi.org/10.1007/BF01478928

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