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.

vhl是 cullin 2 ring-vhl e3连接酶的底物识别亚基，参与泛素-蛋白酶体系统，主要功能是降解缺氧诱导因子α亚基（ hif-α ），发挥肿瘤抑制作用。基于vhl与hifs的相互作用，开发出了蛋白水解靶向嵌合体（protacs），其可诱导靶蛋白降解。

2015年3月3日 · To achieve this, VHL binds HIFα and recruits it to a specific E3 ubiquitin ligase complex, a Cullin-RING-ligase. In this issue of Structure, Nguyen et al. provide a structural view of how VHL engages the ligase in order to inhibit the hypoxic response.

2015年3月3日 · Our structure provides a structural basis for the study of the pathogenesis of VHL disease and rationale for the design of novel compounds that may modulate cullin-substrate receptor interactions. Cullin-RING E3 ubiquitin ligases (CRLs) are critical for targeting cellular proteins for ubiquitin-dependent degradation through the 26S proteasome.

2009年11月26日 · 本文选择RING家族中与p53相互作用的MDM2、 COP1、Pirh2进行了结构预测，并研究了这三个蛋白与泛素蛋白（Ub）的结合、 高能位点及其作用。 对于分类较明确、序列较齐全的Cullins家族，本文从动物中. 选取了172条序列，构建了Cullins家族及各亚家族的系统发育树。 除此之外，本. 文还将现存的所有cullin家族序列进行收集和比对，确定了各家族之间关系以及. 关键的位点。 关键词. E3连接酶，RING家族，结构预测，泛素蛋白，Cullins家族，系统发育 …

2009年11月1日 · In this article we discuss the genetic function, molecular assembly and substrates of CUL4–RING ligases (CRL4s). We compare the pleiotropic functions of CUL4 across several species and review the current model for CUL4 assembly with its linker protein DDB1 (for damaged DNA binding) and its family of WD40-containing substrate receptors.

CRL2 (VHL) and CRL4 (CRBN) are two key E3 ligases for small molecule PROTACs. Currently, owing to the incurability of malignant diseases, all evidence regarding VHL-based PROTACs is tumor associated, which serve as potential anti-cancer interventions .

2015年3月3日 · The von Hippel-Lindau tumor suppressor protein (VHL) recruits a Cullin 2 (Cul2) E3 ubiquitin ligase to downregulate HIF-1α, an essential transcription factor for the hypoxia response. Mutations in VHL lead to VHL disease and renal cell carcinomas.

Hypoxia inducible factor (HIF)-mediated response to hypoxic conditions is turned off by VHL-mediated ubiq-uitination of HIFa. To achieve this, VHL binds HIF and recruits it to a specific E3 ubiquitin ligase complex, a. Cullin-RING-ligase. In this issue of , Nguyen et al. provide a structural view of how VHL engages the.

2021年5月27日 · In our in vitro assays, the recombinant CUL2•RBX1 purified from either expression system can catalyze the conjugation of NEDD8 to CUL2 and can bind VHL•EloB/C to form CRL2 VHL that ...