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Selective Formation of AAB‐ and ABC‐Type Heterotrimeric α‐Helical Coiled Coils
Author(s) -
Kiyokawa Tomohiro,
Kanaori Kenji,
Tajima Kunihiko,
Kawaguchi Masataka,
Mizuno Toshihisa,
Oku Junichi,
Tanaka Toshiki
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305729
Subject(s) - heterotrimeric g protein , coiled coil , chemistry , random coil , peptide , stereochemistry , amino acid , crystallography , circular dichroism , biochemistry , g protein , receptor
The α‐helical coiled coils have a representative amino acid sequence of ( abcdefg ) n heptad repeats. We previously reported that two peptides named IZ‐2A and IZ‐2W formed an (IZ‐2A) 2 /IZ‐2W heterotrimer with an Ala–Ala–Trp interaction in the hydrophobic core. In this paper, we describe the selective formation of AAB‐ and ABC‐type heterotrimers. To increase the selectivity of the AAB‐type heterotrimeric formation, Lys residues at the f position were mutated to either an Ala or a Gln residue to form IZ‐2A( f A) or IZ‐2W( f Q). Separately, both IZ‐2A( f A) and IZ‐2W( f Q) have a random structure at pH 7 and 20 °C. However, together IZ‐2A( f A) and IZ‐2W( f Q) form a 2:1 complex with a thermal transition midpoint ( T m) of 48 °C. This procedure was applied to prepare the ABC‐type heterotrimer, in which two sets of Ala–Ala–Trp interactions were designed in the hydrophobic core. Interhelical interaction between the e and g positions and the α‐helical propensity of the amino acid at the f position were also considered in the design. The resultant three peptides selectively formed the ABC‐type heterotrimer with a T m of 51 °C. Other peptide combinations had random coil properties.