MYELOID CELL LEUKEMIA PROTEIN 1 BOUND TO BIM-BH3 PEPTIDE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。巴克是Bcl-2蛋白家族中的执行者。它的功能通常被Bcl-2同源物Mcl-1拮抗，而Mcl-1功能本身被所谓的仅BH 3蛋白拮抗，该蛋白将各种应激刺激传递到凋亡机制。细胞在接受合适的刺激例如DNA损伤后经历凋亡。这导致仅BH 3蛋白的释放，其直接或间接地激活巴克（和Bax）。在释放BH 3-only蛋白后，巴克和Bax经历结构转变（和可能的寡聚化），并随后诱导线粒体膜透化（MMP）。MMP代表细胞在凋亡途径上的不归点，并且对于随后的细胞死亡至关重要。具有同源BH 3肽配体的Mcl-1晶体在实验室源上将X射线抑制到2.0 A，但已证明分子置换是难治的。我们希望对与BH 3肽复合的硒-甲硫氨酸掺入的Mcl-1晶体进行MAD实验

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bak is a member of the executioner-faction of the Bcl-2 protein family. Its function is normally antagonised by the Bcl-2 homologue Mcl-1, and Mcl-1 function is itself antagonised by the so-called BH3-only proteins that transmit various stress stimuli to the apoptotic machinery. Cells undergo apoptosis after receiving suitable stimuli such as e.g. DNA damage. This results in release of BH3-only proteins which, directly or indirectly, activate Bak (and Bax). Following release of BH3-only proteins, Bak and Bax undergo a structural transition (and probably oligomerization), and subsequently induce mitochondrial membrane permeabilisation (MMP). MMP represents the ¿¿¿point of no return¿¿¿ for a cell on the apoptosis pathway, and is of critical importance for subsequent cell death. Crystals of Mcl-1 with cognate BH3 peptide ligands diffract X-rays on a laboratory source to 2.0 A, but have proven refractory to molecular replacement. We wish to perform a MAD experiment on crystals of seleno-methionine incorporated Mcl-1 complexed with BH3 peptide