Choi Jay H, Govaerts Cedric, May Barnaby C H, Cohen Fred E
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
Proteins. 2008 Oct;73(1):150-60. doi: 10.1002/prot.22051.
The left-handed parallel beta-helix (LbetaH) is a structurally repetitive, highly regular, and symmetrical fold formed by coiling of elongated beta-sheets into helical "rungs." This canonical fold has recently received interest as a possible solution to the fibril structure of amyloid and as a building block of self-assembled nanotubular structures. In light of this interest, we aimed to understand the structural requirements of the LbetaH fold. We first sought to determine the sequence characteristics of the repeats by analyzing known structures to identify positional preferences of specific residues types. We then used molecular dynamics simulations to demonstrate the stabilizing effect of successive rungs and the hydrophobic core of the LbetaH. We show that a two-rung structure is the minimally stable LbetaH structure. In addition, we defined the structure-based sequence preference of the LbetaH and undertook a genome-wide sequence search to determine the prevalence of this unique protein fold. This profile-based LbetaH search algorithm predicted a large fraction of LbetaH proteins from microbial origins. However, the relative number of predicted LbetaH proteins per specie was approximately equal across the genomes from prokaryotes to eukaryotes.
左手平行β-螺旋（LbetaH）是一种由细长的β-折叠片卷曲成螺旋状“梯级”形成的结构重复、高度规则且对称的折叠结构。这种典型的折叠结构最近受到关注，因为它可能是淀粉样蛋白纤维结构的一种解决方案，也是自组装纳米管结构的构建单元。鉴于此，我们旨在了解LbetaH折叠的结构要求。我们首先通过分析已知结构来确定重复序列的特征，以识别特定残基类型的位置偏好。然后，我们使用分子动力学模拟来证明连续梯级和LbetaH疏水核心的稳定作用。我们表明，双梯级结构是最小稳定的LbetaH结构。此外，我们定义了基于结构的LbetaH序列偏好，并进行了全基因组序列搜索，以确定这种独特蛋白质折叠的普遍性。这种基于轮廓的LbetaH搜索算法预测了很大一部分来自微生物的LbetaH蛋白。然而，从原核生物到真核生物的基因组中，每个物种预测的LbetaH蛋白相对数量大致相等。
