Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates
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Roy A. Mariuzza
Abstract
Adaptive immunity in jawless vertebrates is mediated by antigen receptors that are fundamentally different from those of jawed vertebrates. Whereas antibodies and T cell receptors (TCRs) are composed of immunoglobulin (Ig) domains, the variable lymphocyte receptors (VLRs) of jawless fish consist of leucine-rich repeat (LRR) modules. As with antibodies and TCRs, VLRs are assembled by DNA recombination in a process that generates a vast repertoire of receptors. VLRs recognize as diverse an array of particulate and soluble antigens as Ig-based antibodies, and do so with similar affinity and specificity. X-ray crystallographic studies of VLRs in complex with protein and carbohydrate antigens have shown that these LRR-based receptors use nearly all their concave surface to bind ligands, in addition to a highly variable loop in their C-terminal LRR capping module. This structural information, combined with a comprehensive analysis of VLR sequences, has revealed an almost perfect match between antigen-contacting positions and positions with highest sequence diversity. The independent evolution approximately 500 million years ago of LRR-based and Ig-based receptors of comparable diversity and antigen-binding properties provides evidence for the survival value of adaptive immunity in vertebrates.
©2010 by Walter de Gruyter Berlin New York
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- Guest Editorial
- Highlight: Of Systems and Structures
- HIGHLIGHT: STRUCTURAL SYSTEMS BIOLOGY
- Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex
- Towards molecular systems biology of gene transcription and regulation
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- The type III secretion injectisome, a complex nanomachine for intracellular ‘toxin’ delivery
- Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates
- The XPD helicase: XPanDing archaeal XPD structures to get a grip on human DNA repair
- Decoding transcription and microRNA-mediated translation control in Drosophila development
- Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis
- PROTEIN STRUCTURE AND FUNCTION
- The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes
- CELL BIOLOGY AND SIGNALING
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- Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway
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- NOVEL TECHNIQUES
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