5w1k
From Proteopedia
JUNV GP1 CR1-10 Fab CR1-28 Fab complex
Structural highlights
FunctionIGK_HUMAN 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:22158414, PubMed:20176268). 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).[1] [2] [3] Publication Abstract from PubMedWhile five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1-Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern. Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.,Clark LE, Mahmutovic S, Raymond DD, Dilanyan T, Koma T, Manning JT, Shankar S, Levis SC, Briggiler AM, Enria DA, Wucherpfennig KW, Paessler S, Abraham J Nat Commun. 2018 May 14;9(1):1884. doi: 10.1038/s41467-018-04271-z. PMID:29760382[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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