Retention of Native Quaternary Structure in Racemic Melittin Crystals
Retention of Native Quaternary Structure in Racemic Melittin Crystals
复制标题
DOI：
10.1021/jacs.9b02691
复制
发表时间：
2019-05-15
影响因子：
15
通讯作者：
Gellman, Samuel H.
中科院分区：
文献类型：
--
作者：
Kurgan, Kathleen W.;Kleman, Adam F.;Gellman, Samuel H.
外消旋晶体学已被用于阐明肽和小蛋白质的二级和三级结构，这些结构与传统的结晶方法不同。然而，目前尚不清楚外消旋晶体学是否可以捕获天然的四级结构，这可能会被异手性协会破坏。我们正在探索使用外消旋晶体学来表征膜相关肽的自组装行为，其中很少有结晶。我们报告的膜活性肽蜂毒肽的外消旋晶体结构，新的结构允许与以前报道的L-蜂毒肽的晶体结构进行比较。在结晶L-蜂毒肽中观察到的四聚体组装已被提出代表该肽在溶液中检测到的四聚体状态。这种四聚体组装在外消旋晶体中精确地再现，这加强了四聚体具有生物学相关性的结论。更广泛地说，这些发现表明外消旋晶体学可以提供对天然四级结构的见解。
Racemic crystallography has been used to elucidate the secondary and tertiary structures of peptides and small proteins that are recalcitrant to conventional crystallization. It is unclear, however, whether racemic crystallography can capture native quaternary structure, which could be disrupted by heterochiral associations. We are exploring the use of racemic crystallography to characterize the self-assembly behavior of membrane-associated peptides, very few of which have been crystallized. We report a racemic crystal structure of the membrane-active peptide melittin; the new structure allows comparison with a previously reported crystal structure of L-melittin. The tetrameric assembly observed in crystalline L-melittin has been proposed to represent the tetrameric state detected in solution for this peptide. This tetrameric assembly is precisely reproduced in the racemic crystal, which strengthens the conclusion that the tetramer is biologically relevant. More broadly, these findings suggest that racemic crystallography can provide insight on native quaternary structure.