Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
J Biol Inorg Chem. 2011 Feb;16(2):257-66. doi: 10.1007/s00775-010-0722-2. Epub 2010 Nov 10.
The ability to form and control both secondary structure and oligomerization in short peptides has proven to be challenging owing to the structural instability of such peptides. The conantokin peptides are a family of γ-carboxyglutamic acid containing peptides produced in the venoms of predatory sea snails of the Conus family. They are examples of short peptides that form stable helical structures, especially in the presence of divalent cations. Both monomeric and dimeric conantokin peptides have been identified and represent a new mechanism of helix association, "the metallozipper motif" that is devoid of a hydrophobic interface between monomers. In the present study, a parallel/antiparallel three-helix bundle was identified and its crystal structure determined at high resolution. The three helices are almost perfectly parallel and represent a novel helix-helix association. The trimer interface is dominated by metal chelation between the three helices, and contains no interfacial hydrophobic interactions. It is now possible to produce stable monomeric, dimeric, or trimeric metallozippers depending on the peptide sequence and metal ion. Such structures have important applications in protein design.
由于这些肽的结构不稳定性，证明在短肽中形成和控制二级结构和寡聚体的能力具有挑战性。芋螺毒素肽是一组在芋螺科捕食性海蜗牛毒液中产生的含有γ-羧基谷氨酸的肽。它们是形成稳定螺旋结构的短肽的示例，特别是在存在二价阳离子的情况下。已经鉴定出单体和二聚体芋螺毒素肽，它们代表了一种新的螺旋缔合机制，即“金属拉链基序”，该基序在单体之间没有疏水性界面。在本研究中，鉴定并确定了高分辨率的平行/反平行三螺旋束的晶体结构。三个螺旋几乎完全平行，代表了一种新颖的螺旋-螺旋缔合。三聚体界面主要由三个螺旋之间的金属螯合作用控制，不包含界面疏水性相互作用。现在可以根据肽序列和金属离子产生稳定的单体、二聚体或三聚体金属拉链。这些结构在蛋白质设计中有重要的应用。
