5xp1

Structure of monomeric mutant of REI immunoglobulin light chain variable domain crystallized at pH 6

spinqualitylabelsall models 5xp1, resolution 2.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xp1 is a 8 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 5b3c. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.88Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KVD33_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:20176268, PubMed:17576170). Publication Abstract from PubMed Amyloid light-chain (AL) amyloidosis is a protein-misfolding disease characterized by accumulation of immunoglobulin light chains (LCs) into amyloid fibrils. Dimerization of a full length or variable domain (VL ) of LC serves to stabilize the native state and prevent the formation of amyloid fibrils. We here analyzed the thermodynamic properties of dimerization and unfolding reactions by nonamyloidogenic VL from REI LC or its monomeric Y96K mutant using sedimentation velocity and circular dichroism. The data indicate that the equilibrium shifts to native dimerization for wild-type REI VL by elevating temperature due to the negative enthalpy change for dimer dissociation (-81.2 kJ.mol-1 ). The Y96K mutation did not affect the stability of the monomeric native state but increased amyloidogenicity. These results suggest that the heat-induced native homodimerization is the major factor preventing amyloid formation by wild-type REI VL . Heat-induced native oligomerization may be an efficient strategy to avoid the formation of misfolded aggregates particularly for thermostable proteins that are used at elevated temperatures under conditions where other proteins tend to misfold. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 5XP1 and 5XQY. Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI.,Nawata M, Tsutsumi H, Kobayashi Y, Unzai S, Mine S, Nakamura T, Uegaki K, Kamikubo H, Kataoka M, Hamada D FEBS J. 2017 Sep;284(18):3114-3127. doi: 10.1111/febs.14181. Epub 2017 Aug 13. PMID:28736891 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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