Pyrin is a cytosolic pattern‐recognition receptor that normally functions as a guard to trigger capase‐1 inflammasome assembly in response to bacterial toxins and effectors that inactivate RhoA. The MEFV gene encoding human pyrin is preferentially expressed in phagocytes. Key domains in pyrin include a pyrin domain (PYD), a linker region, and a B30.2 domain. Binding of ASC to pyrin by a PYD‐PYD interaction triggers inflammasome assembly. Pyrin is held in an inactive conformation by negative regulation mechanisms to avoid premature inflammasome assembly. One mechanism of negative regulation involves phosphorylation of the linker by PRK kinase which in turn is positively regulated by active RhoA. The B30.2 domain also negatively regulates pyrin. Gain of function mutations in MEFV responsible for the autoinflammatory disease Familial Mediterranean Fever (FMF) map to exon 10 encoding the B30.2 domain. Insights into pyrin regulation have come from studies of several Yersinia effectors, which are injected into phagocytes and interact with the RhoA‐PRK‐pyrin axis during infection. Two effectors, YopE and YopT, inactivate RhoA to disrupt phagocytic signaling. To counteract an effector‐triggered immune response, a third effector, YopM, binds to and inhibits pyrin by hijacking PRK and RSK and directing linker phosphorylation. Inhibition of pyrin by YopM is required for virulence of Yersinia pestis, the agent of plague. Recent results from infection studies with human phagocytes and mice producing pyrin B30.2 FMF variants show that gain of function MEFV mutations bypass inhibition by YopM. Population genetic data suggest that MEFV mutations were selected for in individuals of Mediterranean decent during historic plague pandemics. This review discusses current concepts of pyrin regulation and its interaction with Yersinia effectors.

中文翻译：

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pyrin 炎症小体和耶尔森氏菌效应物相互作用。

Pyrin 是一种细胞溶质模式识别受体，通常作为一种保护装置来触发 capase-1 炎性体组装，以响应使 RhoA 失活的细菌毒素和效应物。编码人pyrin的MEFV基因优先在吞噬细胞中表达。pyrin 中的关键域包括一个 pyrin 域 (PYD)、一个连接区和一个 B30.2 域。通过 PYD-PYD 相互作用将 ASC 与 pyrin 结合触发炎症小体组装。Pyrin 通过负调节机制保持在非活性构象中，以避免过早的炎症小体组装。负调控的一种机制涉及 PRK 激酶对接头的磷酸化，而 PRK 激酶又受到活性 RhoA 的正调控。B30.2 域也负调控 pyrin。MEFV功能突变的获得负责自身炎症性疾病家族性地中海热 (FMF) 映射到编码 B30.2 域的外显子 10。对 pyrin 调节的见解来自对几种耶尔森氏菌效应物的研究，这些效应物被注入吞噬细胞并在感染过程中与 RhoA-PRK-pyrin 轴相互作用。两个效应器 YopE 和 YopT 使 RhoA 失活以破坏吞噬信号。为了抵消效应子触发的免疫反应，第三个效应子 YopM 通过劫持 PRK 和 RSK 并指导连接子磷酸化来结合并抑制 pyrin。鼠疫耶尔森菌（鼠疫的病原体）的毒力需要 YopM 抑制 pyrin 。对人类吞噬细胞和产生 pyrin B30.2 FMF 变体的小鼠的感染研究的最新结果表明，MEFV功能的获得突变绕过YopM的抑制。人口遗传数据表明，在历史性瘟疫大流行期间，地中海地区的个体选择了MEFV突变。本综述讨论了 pyrin 调节的当前概念及其与耶尔森氏菌效应物的相互作用。