Rotational and hinge dynamics of discoidal high density lipoproteins probed by interchain disulfide bond formation

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• 作者：Ling Li^a ; ^b ; ¹ ; ^lil@umn.edu ; Songlin Li^a ; Martin K. Jones^a ; ^c ; Jere P. Segrest^a ; ^c ; ¹ ; ^{segrest@uab.edu}
• 关键词：apo ; apolipoprotein ; apoA-I/HDL ; reconstituted HDL ; DMPC ; dimyristoylphosphatidylcholine ; HDL ; high density lipoproteins ; LL5/5 ; double belt rotamer forming a pairwise helix 5 domain ; LL5/6 ; double belt rotamer forming pairwise helix 5/6 domains ; LL5/4 ; d
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2012
• 出版时间：March, 2012
• 年：2012
• 卷：1821
• 期：3
• 页码：481-489
• 全文大小：1440 K

文摘

To develop a detailed double belt model for discoidal HDL, we previously scored inter-helical salt bridges between all possible registries of two stacked antiparallel amphipathic helical rings of apolipoprotein (apo) A-I. The top score was the antiparallel apposition of helix 5 with 5 followed closely by appositions of helix 5 with 4 and helix 5 with 6. The rationale for the current study is that, for each of the optimal scores, a pair of identical residues can be identified in juxtaposition directly on the contact edge between the two antiparallel helical belts of apoA-I. Further, these residues are always in the ?th position?in one of the eighteen 11-mer repeats that make up the lipid-associating domain of apoA-I. To illustrate our terminology, 129j (LL5/5) refers to the juxtaposition of the C¦Á atoms of G129 (in a ?th position? in the pairwise helix 5 domains. We reasoned that if identical residues in the double belt juxtapositions were mutated to a cysteine and kept under reducing conditions during disc formation, we would have a precise method for determining registration in discoidal HDL by formation of a disulfide-linked apoA-I homodimer. Using this approach, we conclude that 129j (LL5/5) is the major rotamer orientation for double belt HDL and propose that the small ubiquitous gap between the pairwise helix 5 portions of the double belt in larger HDL discoidal particles is significantly dynamic to hinge off the disc edge under certain conditions, e.g., in smaller particles or perhaps following binding of the enzyme LCAT. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).