Chameleon peptide

From Proteopedia

Does the amino acid sequence really determine the 3D structure of a peptide?

Chamelion

1 General question
2 Methodology
3 Seeing is believing
4 3D structure of a sequence adopts to its environment

General question

To determine the extent to which non-local factors influence the formation of secondary structural elements

Methodology

Design the longest possible sequence that can fold into an alpha-helix when inserted into one place in a protein sequence and a beta-sheet when inserted into another. Two key references are: on a Chameleon peptide^[1] and an analysis of Helix-to-Strand Transition Between Peptides with Identical Sequences^[2].

Seeing is believing

To simplify the figure, the entire IgG-Binding domain^[3] is colored beige. Now, if the amino acids residues, <23-33>, are changed to the Chameleon sequence i.e. AWTVEKAFKTF, virtually no change in structure is seen. Specifically the WT sequence in yellow (residues 23-33) is changed to Chameleon sequence shown in pink, , n.b. only 5 AA's have been changed in this region

WT: TTYKLILNGKTLKGETTTEAVDAATAEKVFKQYANDNGVDGEWTYDDATKTFTVTEK
Mutated: TTYKLILNGKTLKGETTTEAVDAWTVEKAFKTFANDNGVDGEWTYDDATKTFTVTEK

If a similar change in the WT sequences is made to the Chameleon sequence for residues 42-52 again virtually no change in the 3D structure of this protein is seen.

WT: TTYKLILNGKTLKGETTTEAVDAATAEKVFKQYANDNGVDGEWTYDDATKTFTVTEK
Mutated: TTYKLILNGKTLKGETTTEAVDAATAEKVFKQYANDNGVDGAWTVEKAFKTFTVTEK

3D structure of a sequence adopts to its environment

The 3D structure of the Chameleon sequence, AWTVEKAFKTF, appears to adopt to its environment.

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Protein G immunoglobulin binding domain (PDB code 2gb1)

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References

↑ Minor DL Jr, Kim PS. Context-dependent secondary structure formation of a designed protein sequence. Nature. 1996 Apr 25;380(6576):730-4. PMID:8614471 doi:http://dx.doi.org/10.1038/380730a0
↑ Zhou X, Alber F, Folkers G, Gonnet GH, Chelvanayagam G. An analysis of the helix-to-strand transition between peptides with identical sequence. Proteins. 2000 Nov 1;41(2):248-56. PMID:10966577
↑ Gronenborn AM, Filpula DR, Essig NZ, Achari A, Whitlow M, Wingfield PT, Clore GM. A novel, highly stable fold of the immunoglobulin binding domain of streptococcal protein G. Science. 1991 Aug 9;253(5020):657-61. PMID:1871600