Abstract
STUDIES of extant protein sequences indicate that amino-acid insertions and deletions are preferentially located in loop regions1, which has traditionally been explained as the result of selection removing deleterious mutations within secondary structural elements from the population. But there is no a priori reason to discount the possibility that insertions within secondary structure could either be tolerated until compensatory mutations arise, or have effects that are propagated away from secondary structure into loops. Earlier studies have indicated that insertions are generally tolerated, although much less well within secondary structure elements than in loop regions2–8. Here we show that amino-acid insertions in an α-helix of T4 lysozyme can be accepted in two different ways. In some cases the inserted amino acids are accommodated within the helix, leading to the translocation of wild-type residues from the helix to the preceding loop. In other cases the insertion causes a ‘looping-out’ in the first or last turn of the helix. The individual structural responses seem to be dominated by the maintenance of the interface between the helix and the rest of the protein.
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References
Pascarella, S. & Argos, P. J. molec. Biol. 224, 461–471 (1992).
Barany, F. Proc. natn. Acad. Sci. U.S.A. 82, 4202–4206 (1985).
Sondek, J. & Shortle, O. Proteins: Struct. Funct. Genet. 7, 299–305 (1990).
Sondek, J. & Shortle, D. Proteins: Struct. Funct. Genet. 13, 132–140 (1992).
Freimuth, P. I., Taylor, J. W. & Kaiser, E. T. J. biol. Chem. 265, 896–901 (1990).
Marti, T., Otto, H., Rösselet, S. J., Heyn, M. P. & Khorana, H. G. Proc. natn. Acad. Sci. U.S.A. 89, 1219–1223 (1992).
Starzyk, R. M., Burbaum, J. J. & Schimmel, P. Biochemistry 28, 8479–8484 (1989).
Ladant, D., Glaser, P. & Ullmann, A. J. biol. Chem. 267, 2244–2250 (1992).
Heinz, D. W., Baase, W. A. & Matthews, B. W. Proc. natn. Acad. Sci. U.S.A. 89, 3751–3755 (1992).
Eriksson, A. E. et al. Science 255, 178–183 (1992).
Gray, T. M. & Matthews, B. W. J. molec. Biol. 175, 75–81 (1984).
Milner-White, E. J. & Poet, R. Trends biochem. Sci. 12, 189–192 (1987).
McIntosh, L. P., Wand, A. J., Lowry, D. F., Redfield, A. G. & Dahlquist, F. W. Biochemistry 29, 6341–6362 (1990).
Lee, B. & Richards, F. M. J. molec. Biol. 55, 379–400 (1971).
Connolly, M. Science 221, 709–713 (1983).
Lesk, A. M. & Chothia, C. J. molec. Biol. 136, 225–270 (1980).
Presta, L. G. & Rose, G. D. Science 240, 1632–1641 (1988).
Bashford, D., Chothia, C. & Lesk, A. M. J. molec. Biol. 196, 199–216 (1987).
Dao-pin, S., Baase, W. A. & Matthews, B.W. Proteins: Struct Funct Genet. 7, 198–204 (1990).
Zhang, X.-J., Baase, W. A. & Matthews, B. W. Biochemistry 30, 2012–2017 (1991).
Becktel, W. J. & Schellman, J. A. Biopolymers 26, 1859–1877 (1987).
Matsumura, M. & Matthews, B. W. Science 243, 792–794 (1989).
Kunkel, T. A., Roberts, J. D. & Zakour, R. A. Meth. Enzym. 154, 367–382 (1987).
Poteete, A. R., Dao-pin, S., Nicholson, H. & Matthews, B. W. Biochemistry 30, 1425–1432 (1991).
Streisinger, G., Mukai, F., Dreyer, W. J., Miller, B. & Horiuchi, S. Cold Spring Harb. Symp. quant. Biol. XXVI, 25–30 (1961).
Weaver, L. H. & Matthews, B. W. J. molec. Biol. 193, 189–199 (1987).
Jancarik, J. & Kim, S.-H. J. appl. Crystallogr. 24, 409–411 (1991).
Alber, T., Dao-pin, S., Nye, J. A., Muchmore, D. C. & Matthews, B. W. Biochemistry 26, 3754–3758 (1987).
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Heinz, D., Baase, W., Dahlquist, F. et al. How amino-acid insertions are allowed in an α-helix of T4 lysozyme. Nature 361, 561–564 (1993). https://doi.org/10.1038/361561a0
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DOI: https://doi.org/10.1038/361561a0
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