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| A BURIED POLAR INTERACTION IMPARTS STRUCTURAL UNIQUENESS IN A DESIGNED HETERODIMERIC COILED-COIL |
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| Author(s): LUMB KJ, KIM PS |
| Source: BIOCHEMISTRY Volume: 34 Issue: 27 Pages: 8642-8648 Published: JUL 11 1995 |
| Times Cited: 242 References: 59 |
| Abstract: Buried polar residues are a common feature of natural proteins. ACID-p1 and BASE-pl are two designed peptides that form a parallel, heterodimeric coiled coil with a fixed tertiary structure [O'Shea, E.K., Lumb, K.J., and Kim, P.S. (1993) Curr. Biol. 3, 658-667]. The interface between the ACID-pl and BASE-pl helices consists of hydrophobic Leu residues, with the exception of a single polar residue, Asn 14. In the crystal structure of the GCN4 leucine zipper coiled coil, an analogous Asn is hydrogen bonded to the corresponding Asn of the opposing helix, thereby forming a buried polar interaction in an otherwise hydrophobic interface between the helices [O'Shea, E. K., Klemm, J. D., Kim, P. S., and Aler, T. (1991) Science 254, 539-544]. This buried polar interaction in the ACID-pl/BBSE-pl heterodimer was removed by substituting Bsn 14 with Leu. The Asn 14 --> Leu variants are significantly more stable than the pi peptides and preferentially form a heterotetramer instead of a heterodimer. Strikingly, the heterotetramer does not fold into a unique structure; in particular, the helices lack a unique orientation. Thus, the Asn 14 residue imparts specificity for formation of a two-stranded, parallel coiled coil at the expense of stability. The results suggest that, whereas nonspecific hydrophobic interactions contribute to protein stability, the requirement to satisfy the hydrogen bonding potential of buried polar residues in the generally hydrophobic environment of the protein interior can impart specificity (structural uniqueness) to protein folding and design. |
| Document Type: Article |
| Language: English |
Addresses:
1. MIT, HOWARD HUGHES MED INST, DEPT BIOL, WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA |
| Publisher: AMER CHEMICAL SOC, PO BOX 57136, WASHINGTON, DC 20037-0136 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: RH991 |
| ISSN: 0006-2960 |
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