BIRC6客户端复合体的结构提供了SMAC介导的体释放机制
Moritz Hunkeler1,2, Cyrus Y Jin1,2, Eric S Fischer1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
概括
抑制细胞灭亡蛋白 (IAP) 调节细胞死亡. 这项研究揭示了BIRC6的结构,解释了SMAC结合如何抑制酶,并提供了对亡调节和癌症治疗的见解.
科学领域:
- 分子生物学
- 结构生物学
- 细胞死亡研究
背景情况:
- 细胞亡的调节对于发育和疾病预防至关重要.
- 抑制细胞灭绝蛋白 (IAP) 控制体,使其成为治疗点.
- 像SMAC和HTRA2这样的线粒体蛋白调节IAP.
研究的目的:
- 阐明BIRC6介导的酶抑制的分子机制.
- 了解SMAC结合如何释放BIRC6的酶抑制.
- 通过亲细胞因子提供IAP调节的结构性见解.
主要方法:
- 全长度人类BIRC6的冷电子显微镜 (冷EM).
- 与SMAC,体和HTRA2复合的BIRC6的结构分析.
主要成果:
- 确定了与SMAC,caspases和HTRA2结合的BIRC6的架构.
- 揭示了BIRC6介导的酶抑制机制.
- 证明了SMAC与BIRC6的几乎不可逆转的结合,解释了其抑制控制.
结论:
- 这项研究提供了对BIRC6在亡中的作用的分子理解.
- SMAC与BIRC6的相互作用突显了细胞死亡途径中的关键调节机制.
- 这些发现为开发针对癌症等疾病的治疗方法提供了潜在的途径.
相关概念视频
Caspases
12.6K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.6K
The Intrinsic Apoptotic Pathway
6.7K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
The Extrinsic Apoptotic Pathway
6.5K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.5K
Assembly of Signaling Complexes
5.8K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.8K
Apoptosis
11.7K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.7K
Intralumenal Vesicles and Multivesicular Bodies
3.6K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.6K


