Motta A, Bremnes B, Morelli M A, Frank R W, Saviano G, Bakke O
Istituto per la Chimica di Molecole di Interesse Biologico del CNR, Napoli, Italy.
J Biol Chem. 1995 Nov 10;270(45):27165-71. doi: 10.1074/jbc.270.45.27165.
The cytosolic tail of the major histocompatibility complex-associated invariant chain protein contains two Leu-based motifs that both mediate efficient sorting to the endocytic pathway. Nuclear magnetic resonance data on a peptide of 27 residues corresponding to the cytosolic tail of human invariant chain indicate that in water at pH 7.4 the membrane distal motif Leu7-Ile8 lies within a nascent helix, while the membrane proximal motif Met16-Leu17 is part of a turn. The presence of a small amount of methanol stabilizes an alpha helix from Gln4 to Leu17 with a kink on Pro15. Point mutations of the cytosolic tail of the protein suggest that amino-terminal residues located in spatial proximity to the Leu motifs contribute to efficient internalization and targeting to endosomes in transfected COS cells. Residues on the spatially opposite side of the Leu motifs were, on the other hand, mutated with no measurable effect on targeting. Structural and biological data thus suggest that the signals are not continuous but consist of "signal patches" formed by the three-dimensional structure of the cytosolic tail of invariant chain.
主要组织相容性复合体相关恒定链蛋白的胞质尾部包含两个基于亮氨酸的基序，二者均介导向胞吞途径的有效分选。关于对应于人恒定链胞质尾部的27个残基肽段的核磁共振数据表明，在pH 7.4的水中，膜远端基序Leu7-Ile8位于新生螺旋内，而膜近端基序Met16-Leu17是转角的一部分。少量甲醇的存在可稳定从Gln4到Leu17的α螺旋，在Pro15处有一个扭结。该蛋白胞质尾部的点突变表明，位于空间上靠近亮氨酸基序的氨基末端残基有助于转染的COS细胞中的有效内化和靶向至内体。另一方面，亮氨酸基序空间相对侧的残基发生突变，对靶向没有可测量的影响。因此，结构和生物学数据表明，信号不是连续的，而是由恒定链胞质尾部的三维结构形成的“信号斑块”组成。
