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Structures and mechanisms of formation of liprotides.
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ( IF 2.5 ) Pub Date : 2020-07-25 , DOI: 10.1016/j.bbapap.2020.140505
Jannik Nedergaard Pedersen 1 , Henriette Kristina Søster Frislev 2 , Jan Skov Pedersen 3 , Daniel Otzen 4
Affiliation  

Many proteins form complexes called liprotides with oleic acid and other cis-fatty acids under conditions where the protein is partially unfolded. The complexes vary in structure depending on the ratio of protein and lipid, but the most common structural organization is the core-shell structure, in which a layer of dynamic, partially unfolded and extended proteins surrounds a micelle-like fatty acid core. This structure, first reported for α-lactalbumin together with OA, resembles complexes formed between proteins and anionic surfactants like SDS. Liprotides first rose to fame through their anti-carcinogenic properties which still remains promising for topical applications though not yet implemented in the clinic. In addition, liprotides show potential in drug delivery thanks to the ability of the micelle core to solubilize and stabilize hydrophobic compounds, though applications are challenged by their sensitivity to acidic pH and dynamic exchange of lipids which makes them easy prey for serum “hoovers” such as albumin. However, liprotides are also of fundamental interest as a generic “protein complex structure”, demonstrating the many and varied structural consequences of protein-lipid interactions. Here we provide an overview of the different types of liprotide complexes, ranging from quasi-native complexes via core-shell structures to multi-layer structures, and discuss the many conditions under which they form. Given the many variable types of complexes that can form, rigorous biophysical analysis (stoichiometry, shape and structure of the complexes) remains crucial for a complete understanding of the mechanisms of action of this fascinating group of protein-lipid complexes both in vitro and in vivo.



中文翻译:

脂肽的结构和形成机理。

许多蛋白质与油酸和其他顺式形成称为脂旋物的复合物-脂肪酸在蛋白质部分展开的条件下。复合物的结构随蛋白质和脂质的比例而异,但最常见的结构组织是核-壳结构,其中一层动态的,部分未折叠和延伸的蛋白质围绕着胶束状脂肪酸核。最早报道α-乳白蛋白和OA的这种结构类似于蛋白质与阴离子表面活性剂(如SDS)之间形成的复合物。Liprotides首先因其抗癌特性而声名fa起,尽管在临床上尚未应用,但对于局部应用仍然有希望。此外,由于胶束核心具有溶解和稳定疏水性化合物的能力,脂肽具有潜在的药物输送能力,尽管应用面临着对酸性pH敏感和脂质动态交换的挑战,这使它们很容易成为血清“白痴”(例如白蛋白)的猎物。然而,脂肽作为一种通用的“蛋白质复合物结构”也具有根本的意义,证明了蛋白质-脂质相互作用的许多不同的结构后果。在这里,我们提供了各种脂肽复合物的概貌,从准天然复合物核-壳结构到多层结构,并讨论它们形成的许多条件。鉴于可以形成多种多样的复合物类型,严格的生物物理分析(化学计量,复合物的形状和结构)对于全面了解这一迷人的蛋白质-脂质复合物在体外体内的作用机理仍然至关重要。。

更新日期:2020-07-30
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