[NMR paper] Architectural rules of the zinc-finger motif: comparative two-dimensional NMR studies

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Architectural rules of the zinc-finger motif: comparative two-dimensional NMR studies of native and "aromatic-swap" domains define a "weakly polar switch".

Related Articles Architectural rules of the zinc-finger motif: comparative two-dimensional NMR studies of native and "aromatic-swap" domains define a "weakly polar switch".

Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8455-9

Authors: Kochoyan M, Keutmann HT, Weiss MA

The Zn-finger motif, encoding a globular minidomain with characteristic structure, provides a striking example of a sequence template for protein folding. Insight into architectural rules relating the amino acid sequence of a protein to its structure and stability may be obtained by comparative study of analogues. As our first step toward defining such rules for the Zn finger, we have recently described the design of an "aromatic-swap" analogue based on the ZFY two-finger repeat: a conserved alternation in sequence pattern observed among odd- and even-numbered domains in a family of sex-related vertebrate transcription factors. Consensus and "swapped" aromatic residues, introduced as revertants of less stable "aromaticless" analogues, were observed to provide equivalent contributions to the thermodynamic stability of the Zn finger. Here we describe and compare the solution structures of a wild-type domain and an aromatic-swap analogue, as determined by two-dimensional NMR and distance-geometry/restrained molecular dynamics calculations. The wild-type and aromatic-swap analogue each contain an N-terminal beta-sheet and a C-terminal alpha-helix (beta beta alpha motif), as observed in other systems, and exhibit a highly ordered hydrophobic core in which the native or swapped aromatic ring is closely packed. Remarkably, however, the two structures are stabilized by alternative aromatic-aromatic interactions, which in turn alter the respective DNA-binding surfaces. Our results suggest that native and swapped Zn-finger sequences encode a "weakly polar switch" between thermodynamically equivalent but functionally distinct architectures for DNA recognition.

PMID: 1924304 [PubMed - indexed for MEDLINE]



Source: PubMed