The third helix of the Antennapedia homeodomain translocates through biological membranes

作者: A. Prochiantz , G. Chassaing , A.H. Joliot , D. Derossi

DOI: 10.1016/S0021-9258(17)34080-2

关键词:

摘要: The 60-amino acid long homeodomain of Antennapedia crosses biological membranes by an energy-independent mechanism, a phenomenon abolished directed mutagenesis within the polypeptide C-terminal region. This finding led us to study internalization several chemically synthesized peptides derived from third helix homeodomain. We report here that 16 amino acids in length corresponding deleted its N-terminal glutamate is still capable translocating through membrane. A longer peptide 20 also translocates, whereas shorter (15 acids) are not internalized cells. As case for entire homeodomain, 20- and 16-amino at 4 degrees C, suggesting mechanism translocation involving classical endocytosis. two translocated can be recovered, intact, cells, strongly they targeted lysosomal compartment. Finally, substitution tryptophans phenylalanines diminishes translocation, raising possibility solely based on general hydrophobicity.

参考文章(23)
B Beaumelle, L Bensammar, A Bienvenüe, Selective translocation of the A chain of diphtheria toxin across the membrane of purified endosomes Journal of Biological Chemistry. ,vol. 267, pp. 11525- 11531 ,(1992) , 10.1016/S0021-9258(19)49942-0
R. Rappuoli, M. Murgia, C. Montecucco, E. Papini, Cell penetration of diphtheria toxin. Reduction of the interchain disulfide bridge is the rate-limiting step of translocation in the cytosol. Journal of Biological Chemistry. ,vol. 268, pp. 1567- 1574 ,(1993) , 10.1016/S0021-9258(18)53890-4
J.X. Jiang, L.A. Chung, E. London, Self-translocation of diphtheria toxin across model membranes. Journal of Biological Chemistry. ,vol. 266, pp. 24003- 24010 ,(1991) , 10.1016/S0021-9258(18)54383-0
J O Moskaug, H Stenmark, S Olsnes, Insertion of diphtheria toxin B-fragment into the plasma membrane at low pH. Characterization and topology of inserted regions. Journal of Biological Chemistry. ,vol. 266, pp. 2652- 2659 ,(1991) , 10.1016/S0021-9258(18)52294-8
Peter Holland, Problems and paradigms: Hoemeobox genes in vertebrate evolution BioEssays. ,vol. 14, pp. 267- 273 ,(1992) , 10.1002/BIES.950140412
W. Gehring, Homeo boxes in the study of development Science. ,vol. 236, pp. 1245- 1252 ,(1987) , 10.1126/SCIENCE.2884726
A. Joliot, C. Pernelle, H. Deagostini-Bazin, A. Prochiantz, Antennapedia homeobox peptide regulates neural morphogenesis Proceedings of the National Academy of Sciences of the United States of America. ,vol. 88, pp. 1864- 1868 ,(1991) , 10.1073/PNAS.88.5.1864
Mark A. Lemmon, John M. Flanagan, Herbert R. Treutlein, Jian Zhang, Donald M. Engelman, Sequence specificity in the dimerization of transmembrane .alpha.-helixes Biochemistry. ,vol. 31, pp. 12719- 12725 ,(1992) , 10.1021/BI00166A002
M. Price, D. Lazzaro, T. Pohl, M-G. Mattei, U. Rüther, J.-C. Olivo, D. Duboule, R. Di Lauro, Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain Neuron. ,vol. 8, pp. 241- 255 ,(1992) , 10.1016/0896-6273(92)90291-K