Retention of α-helical structure by HDL mimetic peptide ATI-5261 upon extensive dilution represents an important determinant for stimulating ABCA1 cholesterol efflux with high efficiency.
Retention of α-helical structure by HDL mimetic peptide ATI-5261 upon extensive dilution represents an important determinant for stimulating ABCA1 cholesterol efflux with high efficiency.
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HDL 模拟肽 ATI-5261 在广泛稀释后保留 α 螺旋结构代表了高效刺激 ABCA1 胆固醇流出的重要决定因素。
DOI：
10.1016/j.bbrc.2013.10.017
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发表时间：
2013
影响因子：
3.1
通讯作者：
Bielicki,JohnK
中科院分区：
文献类型：
--
作者：
Zheng,Ying;Patel,ArtiB;Narayanaswami,Vasanthy;Bielicki,JohnK
ATI-5261是一种新型的单螺旋肽，其刺激细胞胆固醇流出的效力与天然载脂蛋白相似（以摩尔计）。目前，我们研究了赋予胆固醇流出活性的肽的结构特征。具有以相反顺序排列的氨基酸或具有单个精氨酸（R）至谷氨酰胺（Q）取代（即R3Q、R14Q或R23Q）的ATI-5261类似物刺激ABCA 1依赖性胆固醇流出，类似于ATI-5261。因此，无论是特定的正电荷残基的存在，也不是他们的特定安排沿着长度的肽是必要的介导胆固醇流出。类似地，由alld-氨基酸组成的肽有效地刺激胆固醇流出，表明促进巨噬细胞的胆固醇流出不需要立体特异性组分。然而，去除两个或更多个带正电荷的残基（R3，14 → Q和R3，14，23 → Q）大大降低了ATI-5261介导细胞胆固醇流出的能力。这伴随着稀释时α-螺旋结构的损失，表明单个肽链的二级结构对于刺激胆固醇流出是重要的。令人惊讶的是，去除两个或更多个带正电荷的残基的肽保留了结合磷脂并采用α-螺旋结构的能力。这些数据表明疏水肽形成两亲性α-螺旋的倾向不足以介导细胞胆固醇流出。有效刺激胆固醇流出需要ATI-5261在稀释后保留α-螺旋结构。
ATI-5261 is a novel, single-helix peptide that stimulates cellular cholesterol efflux with high potency similar to native apolipoproteins on a molar basis. Presently we investigated structural features of the peptide that conferred cholesterol efflux activity. Analogs of ATI-5261 with amino acids arranged in reverse order or with individual arginine (R) to glutamine (Q) substitutions (i.e. R3Q, R14Q, or R23Q) stimulated ABCA1 dependent cholesterol efflux similar to ATI-5261. Consequently, neither the presence of specific positively charged residues nor their specific arrangement along the length of the peptide was necessary for mediating cholesterol efflux. Similarly, peptides composed of alld-amino acids stimulated cholesterol efflux efficiently, indicating a stereospecific component was not required for promotion of cholesterol efflux from macrophages. Removal of two or more positively charged residues (R3, 14 → Q and R3, 14, 23 → Q) however, greatly reduced the ability of ATI-5261 to mediate cellular cholesterol efflux. This was accompanied by a loss of α-helical structure upon dilution, indicating the secondary structure of individual peptide strands was important for stimulating cholesterol efflux. Surprisingly, peptides with removal of two or more positively charged residues retained the ability to bind phospholipid and adopt an α-helical structure. These data indicate that the propensity of a hydrophobic peptide to form an amphipathic α-helix is not sufficient to mediate cellular cholesterol efflux. Efficient stimulation of cholesterol efflux requires that ATI-5261 retain α-helical structure upon dilution.
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DOI：
10.1161/01.atv.0000165694.39518.95
发表时间：
2005-07-01
影响因子：
8.7
作者：
Navab, M;Anantharamaiah, GM;Fogelman, AM
通讯作者：
Fogelman, AM
影响因子：
2.9
作者：
Vedhachalam, Charulatha;Narayanaswami, Vasanthy;Bielicki, John K.
通讯作者：
Bielicki, John K.
载脂蛋白 A-II 和 A-I 募集细胞磷脂和胆固醇：形成新生载脂蛋白特异性 HDL，其大小、磷脂组成和与 LCAT 的反应性不同。
影响因子：
6.5
作者：
Forte,TM;Bielicki,JK;Goth-Goldstein,R;Selmek,J;McCall,MR
通讯作者：
McCall,MR
影响因子：
6.5
作者：
Tang, CR;Vaughan, AM;Oram, JF
通讯作者：
Oram, JF
影响因子：
6.5
作者：
J. Bielicki;M. McCall;T. Forte
通讯作者：
J. Bielicki;M. McCall;T. Forte