Membrane protein oligomers by design In recent years, soluble protein design has achieved successes such as artificial enzymes and large protein cages. Membrane proteins present a considerable design challenge, but here too there have been advances, including the design of a zinc-transporting tetramer. Lu et al. report the design of stable transmembrane monomers, homodimers, trimers, and tetramers with up to eight membrane-spanning regions in an oligomer. The designed proteins adopted the target oligomerization state and localized to the predicted cellular membranes, and crystal structures of the designed dimer and tetramer reflected the design models. Science, this issue p. 1042 Artificially designed, stable, multitopic membrane proteins localize to the plasma membrane in bacteria and in mammalian cells. The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer—a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices—are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions.

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多通道跨膜蛋白的精确计算设计

膜蛋白寡聚体设计近年来，可溶性蛋白设计取得了成功，如人工酶和大蛋白笼。膜蛋白提出了相当大的设计挑战，但在这方面也取得了进展，包括锌转运四聚体的设计。卢等人。报告了稳定的跨膜单体、同型二聚体、三聚体和四聚体的设计，在低聚物中具有多达八个跨膜区域。设计的蛋白质采用目标寡聚化状态并定位于预测的细胞膜，设计的二聚体和四聚体的晶体结构反映了设计模型。科学，这个问题 p。1042 人工设计的、稳定的、多主题的膜蛋白定位于细菌和哺乳动物细胞的质膜。具有多个跨膜区域的跨膜蛋白的计算设计仍然是一项重大挑战。我们报告了跨膜单体、同源二聚体、三聚体和四聚体的设计，具有 76 到 215 个残基亚基，包含两到四个跨膜区域和多达 860 个在洗涤剂溶液中采用目标寡聚化状态的总残基。设计的蛋白质定位在细菌和哺乳动物细胞的质膜上，膜中的磁性镊子展开实验表明它们非常稳定。设计的二聚体和四聚体的晶体结构——一种火箭形结构，具有宽阔的细胞质基础，漏斗成八个跨膜螺旋——与设计模型非常接近。我们的结果为设计具有新功能的多跨膜蛋白铺平了道路。