Glycolipid transfer proteins (GLTPs) originally were identified as small (~24 kDa), soluble, amphitropic proteins that specifically accelerate the intermembrane transfer of glycolipids. GLTPs and related homologs now are known to adopt a unique, helically dominated, two-layer ‘sandwich’ architecture defined as the GLTP-fold that provides the structural underpinning for the eukaryotic GLTP superfamily. Recent advances now provide exquisite insights into structural features responsible for lipid headgroup selectivity as well as the adaptability of the hydrophobic compartment for accommodating hydrocarbon chains of differing length and unsaturation. A new understanding of the structural versatility and evolutionary premium placed on the GLTP motif has emerged. Human GLTP-motifs have evolved to function not only as glucosylceramide binding/transferring domains for phosphoinositol 4-phosphate adaptor protein-2 during glycosphingolipid biosynthesis but also as selective binding/transfer proteins for ceramide-1-phosphate. The latter, known as ceramide-1-phosphate transfer protein, recently has been shown to form GLTP-fold while critically regulating Group-IV cytoplasmic phospholipase A2 activity and pro-inflammatory eicosanoid production.

中文翻译：

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由 GLTP 折叠定义的鞘脂转移蛋白


糖脂转移蛋白 (GLTP) 最初被鉴定为小 (~24 kDa)、可溶性、两性蛋白质，可特异性加速糖脂的膜间转移。现在已知 GLTP 和相关同源物采用独特的、螺旋主导的、两层“三明治”结构，定义为 GLTP 折叠，为真核 GLTP 超家族提供结构基础。最近的进展现在为负责脂质头基选择性的结构特征以及疏水室适应不同长度和不饱和度的烃链的适应性提供了深刻的见解。人们对 GLTP 基序的结构多功能性和进化优势有了新的认识。人类 GLTP 基序已进化为不仅在鞘糖脂生物合成过程中充当磷酸肌醇 4-磷酸衔接蛋白 2 的葡萄糖基神经酰胺结合/转移结构域，而且还充当神经酰胺-1-磷酸的选择性结合/转移蛋白。后者被称为神经酰胺-1-磷酸转移蛋白，最近已被证明可以形成 GLTP 折叠，同时严格调节 IV 族细胞质磷脂酶 A2 活性和促炎类二十烷酸的产生。