1mcw
From Proteopedia
THREE-DIMENSIONAL STRUCTURE OF A HYBRID LIGHT CHAIN DIMER. PROTEIN ENGINEERING OF A BINDING CAVITY
Structural highlights
FunctionLV208_HUMAN V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAn attempt was made to engineer a binding site and check its structure by X-ray analysis. Two human light chains (Mcg and Weir), with "variable" domain sequences differing in 36 positions, were hybridized into a heterologous dimer and crystallized in ammonium sulfate by the same procedure used for the trigonal form of the Mcg dimer. The three-dimensional structure of the hybrid was determined at 3.5-A resolution by difference Fourier analysis, interactive model building with computer graphics and crystallographic refinement. In the heterologous dimer, the Weir protein behaved as the structural analog of the heavy chain in an antigen binding fragment, while the Mcg protein assumed the role of the light chain component. The hybrid and the Mcg dimer were closely similar in overall structure, an observation probably correlated with the deliberate cleavage of the intrachain disulfide bond in the variable domain of the Weir protein during the hybridization procedure. Examination of the crystal structure of the hybrid suggested that the cleavage resulted in the relaxation of restraints which might otherwise have interfered with the formation of an Mcg-like dimer. There were six substitutions among the residues lining the binding cavities of the hybrid and Mcg dimer. These substitutions significantly affected the sizes, shapes and binding properties of the two cavities. Three-dimensional structure of a hybrid light chain dimer: protein engineering of a binding cavity.,Ely KR, Herron JN, Edmundson AB Mol Immunol. 1990 Feb;27(2):101-14. PMID:2108322[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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