Solid-state nuclear magnetic resonance measurements of HIV fusion peptide to lipid distances reveal the intimate contact of beta strand peptide with membranes and the proximity of the Ala-14-Gly-16 region with lipid headgroups.
Solid-state nuclear magnetic resonance measurements of HIV fusion peptide to lipid distances reveal the intimate contact of beta strand peptide with membranes and the proximity of the Ala-14-Gly-16 region with lipid headgroups.
复制标题
HIV 融合肽与脂质距离的固态核磁共振测量揭示了 β 链肽与膜的紧密接触以及 Ala-14-Gly-16 区域与脂质头基的接近。
DOI：
10.1021/bi6024808
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
Weliky,DavidP
中科院分区：
文献类型：
--
作者：
Qiang,Wei;Yang,Jun;Weliky,DavidP
人类免疫缺陷病毒(HIV)感染始于病毒和宿主细胞膜之间的融合，并由HIV gp41融合蛋白催化。Gp41的∼20N端非极性残基被称为HIV融合肽，它与宿主细胞膜相互作用，在融合过程中起着关键作用。本研究探讨了含有HFP序列的多肽(AVGIGALFLGFLGAAGSTMGARS)在只含磷脂或含磷脂和胆固醇的样品中的膜定位。检测了四个HFP，每个HFP在G5和G16之间的三个序列残基上含有13CO标记。~(13)CO化学位移表明，在样品中，HFP的β链构象比标记残基占优势。用固体核磁共振旋转回波双共振实验测量了HFP~(13)CO基团与Lipid31P原子的核间距。在A14和G16之间标记的HFP的最短13CO−31P距离为5−6ä，并与β链HFP与膜的紧密结合相关。这些结果与在A6或A14用13CO标记的HFPS的测量结果一致。据我们所知，这些数据是首次测量HIV融合肽核与脂质P之间的距离，并提出了与实验数据相一致的寡聚β链HFP膜位置的定性模型。观察到β链HFP与膜的密切接触为进一步研究这种构象的结构与融合活性之间的关系提供了理论基础。
Human immunodeficiency virus (HIV) infection begins with fusion between viral and host cell membranes and is catalyzed by the HIV gp41 fusion protein. The ∼20 N-terminal apolar residues of gp41 are called the HIV fusion peptide (HFP), interact with the host cell membrane, and play a key role in fusion. In this study, the membrane location of peptides which contained the HFP sequence (AVGIGALFLGFLGAAGSTMGARS) was probed in samples containing either only phospholipids or phospholipids and cholesterol. Four HFPs were examined which each contained13CO labeling at three sequential residues between G5 and G16. The13CO chemical shifts indicated that HFP had predominant β strand conformation over the labeled residues in the samples. The internuclear distances between the HFP13CO groups and the lipid31P atoms were measured using solid-state nuclear magnetic resonance rotational-echo double-resonance experiments. The shortest13CO−31P distances of 5−6 Å were observed for HFP labeled between A14 and G16 and correlated with intimate association of β strand HFP and membranes. These results were confirmed with measurements using HFPs singly labeled with13CO at A6 or A14. To our knowledge, these data are the first measurements of distances between HIV fusion peptide nuclei and lipid P, and qualitative models of the membrane location of oligomeric β strand HFP which are consistent with the experimental data are presented. Observation of intimate contact between β strand HFP and membranes provides a rationale for further investigation of the relationship between structure and fusion activity for this conformation.