Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
Biochim Biophys Acta Biomembr. 2019 Jun 1;1861(6):1135-1151. doi: 10.1016/j.bbamem.2019.02.006. Epub 2019 Feb 23.
In all eukaryotic cells, P4 ATPases, also named phospholipid flippases, generate phospholipid asymmetry across biological membranes. This process is essential for cell survival, as it is required for vesicle budding and fusion in the secretory pathway. Several P4 ATPase isoforms can be identified in all sequenced eukaryotic genomes, but their evolution and interrelationships are poorly described. In this study, we conducted a thorough phylogenetic analysis of P4 ATPases in all major eukaryotic super-groups and found that they can be divided into three distinct families, P4A, P4B and P4C ATPases, all of which have an ancient origin. While P4B ATPases have been lost in plants, P4A ATPases are present in all eukaryotic super-groups. P4C ATPases form an intermediate group between the other two but appear to share a common origin with P4A ATPases. Sequence motifs unique to P4 ATPases are situated in the basal ATP hydrolyzing machinery. In addition, no clear signature motifs within P4 ATPase subgroups were found that could be related to lipid specificity, likely pointing to an elaborate transport mechanism in which different amino acid residue combinations in these pumps can result in recognition of the same substrate.
在所有真核细胞中，P4 ATP 酶，也称为磷脂翻转酶，在生物膜上产生磷脂的不对称性。这个过程对于细胞的存活至关重要，因为它是分泌途径中囊泡出芽和融合所必需的。在所有已测序的真核生物基因组中都可以识别出几种 P4 ATP 酶同工型，但它们的进化和相互关系描述得很差。在这项研究中，我们对所有主要的真核超组中的 P4 ATP 酶进行了全面的系统发育分析，发现它们可以分为三个不同的家族，P4A、P4B 和 P4C ATP 酶，所有这些家族都具有古老的起源。虽然 P4B ATP 酶在植物中已经丢失，但 P4A ATP 酶存在于所有真核超组中。P4C ATP 酶在其他两种酶之间形成一个中间组，但似乎与 P4A ATP 酶具有共同的起源。P4 ATP 酶特有的序列基序位于基本的 ATP 水解机制中。此外，在 P4 ATP 酶亚组中没有发现与脂质特异性相关的明确特征基序，这可能表明存在一种复杂的运输机制，其中这些泵中的不同氨基酸残基组合可以识别相同的底物。
