2017年6月6日 · Here, we present the first crystal structure of the CRL2 VHL complex to 3.9 Å resolution, revealing for the first time the full-length Cul2 interacting with Rbx1, which provides insights to the mechanism of the E3 ligase activity. We complement our study with biophysical data on CRL2 VHL PPIs, revealing the basis for Cul2 versus Cul5 recognition.

2024年10月11日 · Here, we show cryo-EM structures of the VHL Cullin 2 RING E3 ligase with the degrader MZ1 directing target protein Brd4 BD2 toward UBE2R1-ubiquitin, and Lys 456 at optimal positioning for nucleophilic attack.

2015年3月3日 · Here, we report the crystal structure of VHL-EloBC bound to an N-terminal domain of Cul2, which reveals how Cul2 recognizes the interface between VHL and EloC. Our results provide insight into how cullins select adaptor proteins and substrate receptors in ECS ubiquitin ligases and establish a structural basis for a better understanding of the ...

2023年7月24日 · Von Hippel-Lindau或VHL是一种E3连接酶，可介导靶蛋白的泛素化和降解。 VHL被认为在肿瘤抑制中起重要作用，特别是由于其与HIF的相互作用。 VHL可用作PROTAC（蛋白水解靶向嵌合体）药物设计，蛋白质降解研究和选择性分析中所需的E3连接酶。

2022年8月8日 · ELOC encodes elongin C, a key component [C] of the VCB-CR complex. The p.Tyr79Cys substitution is a mutational hotspot in sporadic VHL-competent RCC and has previously been shown to mimic the effects of pVHL deficiency on hypoxic signalling.

2017年6月6日 · Here we present the crystal structure of a pentameric CRL2 VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation.

2022年8月23日 · ELOC encodes elongin C, a key component [C] of the VCB-CR complex. The p.Tyr79Cys substitution is a mutational hotspot in sporadic VHL-competent RCC and has previously been shown to mimic the effects of pVHL deficiency on hypoxic signalling.

2014年10月22日 · Mutations in VHL lead to VHL disease and renal cell carcinomas. Inhibition of this pathway to upregulate erythropoietin production is a promising new therapy to treat ischemia and chronic anemia. Here, we report the crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and Elongin C (EloC).

2023年7月24日 · Von Hippel-Lindau或VHL是一种E3连接酶，可介导靶蛋白的泛素化和降解。 VHL被认为在肿瘤抑制中起重要作用，特别是由于其与HIF的相互作用。 VHL可用作PROTAC（蛋白水解靶向嵌合体）药物设计，蛋白质降解研究和选择性分析中所需的E3连接酶。

We identified fragments binding at the ElonginC:Cullin2 interface and a new cryptic pocket in VHL, along with other potential ligandable sites predicted computationally and found to bind solvent molecules in crystal structures. The elucidated interactions provide starting points for …