HFIP-induced structures and assemblies of the peptides from the transmembrane domain 4 of membrane protein Nramp1.
HFIP-induced structures and assemblies of the peptides from the transmembrane domain 4 of membrane protein Nramp1.
复制标题
HFIP 诱导膜蛋白 Nramp1 跨膜结构域 4 的肽的结构和组装。
作者：
Rong Xue;Shuo Wang;Chunyu Wang;Tao Zhu;Fei Li;Hongzhe Sun
膜蛋白 Nramp1（天然抗性相关巨噬细胞蛋白 1）是一种 pH 依赖性二价金属阳离子转运蛋白，可调节感染性和自身免疫性疾病中巨噬细胞的活化。 Nramp1 跨膜结构域 4 (TM4) 内的第 169 位 (G169D) 天然存在的甘氨酸替换为天冬氨酸，使小鼠易受杜氏利什曼原虫、鼠伤寒沙门氏菌和牛分枝杆菌的影响。在这里，我们通过核磁共振（NMR）光谱对两种合成的24残基肽（分别对应于小鼠Nramp1及其G169D突变体的TM4）在1,1,1,3,3,3-六氟异丙醇-d(2)（HFIP-d(2)）水溶液中进行结构和自组装研究。结果表明，野生型肽的残基Ile173至Tyr187以及G169D突变体的残基Trp168至Tyr187分别形成两亲性α螺旋结构。对于野生型肽，N 末端从 Leu167 到 Leu172 的片段结构较差，而对于 G169D 突变体，其结构明确。两种肽聚集形成四聚体，并且肽束中的单体肽在结构和方向上相似。组装中与残基 Phe180-Leu184 相关的 C 端区域中的分子间相互作用可能比这两种肽的中心螺旋片段中的分子间相互作用更强。 G169D 突变可能会改变组装末端开口的大小。
Membrane protein Nramp1 (natural resistance-associated macrophage protein 1) is a pH-dependent divalent metal cation transporter that regulates macrophage activation in infectious and autoimmune diseases. A naturally occurring glycine to aspartic acid substitution at position 169 (G169D) within the transmembrane domain 4 (TM4) of Nramp1 makes mice susceptible to Leishmania donovani, Salmonella typhimurium, and Mycobacterium bovis. Here we present a structural and self-assembling study on two synthetic 24-residue peptides, corresponding to TM4 of mouse Nramp1 and its G169D mutant, respectively, in 1,1,1,3,3,3-hexafluoroisopropanol-d(2) (HFIP-d(2)) aqueous solution by nuclear magnetic resonance (NMR) spectroscopy. The results show that amphipathic alpha-helical structures are formed from residue Ile173 to Tyr187 for the wild-type peptide and from Trp168 to Tyr187 for the G169D mutant, respectively. The segment of the N-terminus from Leu167 to Leu172 is poorly structured for the wild-type peptide, whereas it is well defined for the G169D mutant. Both peptides aggregate to form a tetramer and the monomeric peptides in peptide bundles are structurally and orientationally similar. The intermolecular interactions in assemblies could be stronger in the C-terminal regions related to residues Phe180-Leu184 than those in the central helical segments for both peptides. The G169D mutation may change the size of the opening on the termini of assembly.
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影响因子：
20.3
作者：
Forbes, JR;Gros, P
通讯作者：
Gros, P
DOI：
10.1073/pnas.92.22.10089
发表时间：
1995-10-24
影响因子：
11.1
作者：
CELLIER, M;PRIVE, G;GROS, P
通讯作者：
GROS, P
DOI：
10.1073/pnas.95.3.1148
发表时间：
1998-02-03
影响因子：
11.1
作者：
Fleming, MD;Romano, MA;Andrews, NC
通讯作者：
Andrews, NC
影响因子：
2.9
作者：
Sreerama, N;Woody, RW
通讯作者：
Woody, RW