MYELOID CELL LEUKEMIA PROTEIN 1 BOUND TO BIM-BH3 PEPTIDE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Bak是Bcl-2蛋白家族的刽子手派系的成员。它的功能通常被Bcl-2同源物Mcl-1拮抗，而Mcl-1的功能本身被所谓的BH3-only蛋白拮抗，该蛋白将各种应激刺激传递给凋亡机制。细胞在受到适当的刺激（如DNA损伤）后发生凋亡。这导致bh3蛋白的释放，直接或间接地激活Bak（和Bax）。在bh3蛋白释放后，Bak和Bax经历结构转变（可能是寡聚化），随后诱导线粒体膜通透性（MMP）。MMP代表了细胞在凋亡途径上的不归路，对随后的细胞死亡至关重要。具有同源BH3肽配体的Mcl-1晶体在实验室源上衍射x射线至2.0 a，但已被证明难以进行分子替换。我们希望对Mcl-1与BH3肽络合的硒蛋氨酸晶体进行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