The coiled-coil trigger site of the rod domain of cortexillin I unveils a distinct network of interhelical and intrahelical salt bridges.
BACKGROUND
The parallel two-stranded alpha-helical coiled coil is the most frequently encountered subunit-oligomerization motif in proteins. The simplicity and regularity of this motif have made it an attractive system to explore some of the fundamental principles of protein folding and stability and to test the principles of de novo design.


RESULTS
The X-ray crystal structure of the 18-heptad-repeat alpha-helical coiled-coil domain of the actin-bundling protein cortexillin I from Dictyostelium discoideum is a tightly packed parallel two-stranded alpha-helical coiled coil. It harbors a distinct 14-residue sequence motif that is essential for coiled-coil formation, and is a prerequisite for the assembly of cortexillin I. The atomic structure reveals novel types of ionic coiled-coil interactions. In particular, the structure shows that a characteristic interhelical and intrahelical salt-bridge pattern, in combination with the hydrophobic interactions occurring at the dimer interface, is the key structural feature of its coiled-coil trigger site.


CONCLUSIONS
The knowledge gained from the structure could be used in the de novo design of alpha-helical coiled coils for applications such as two-stage drug targeting and delivery systems, and in the design of coiled coils as templates for combinatorial helical libraries in drug discovery and as synthetic carrier molecules.
Burkhard
P
P
M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Basel, CH-4056, Switzerland. Peter.Burkhard@unibas.ch.
Kammerer
R A
RA
Steinmetz
M O
MO
Bourenkov
G P
GP
Aebi
U
U
D018360:Crystallography, X-Ray; D016350:Leucine Zippers; D008840:Microfilament Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D015800:Protozoan Proteins; D012492:Salts / Q000737:chemistry
D008840:Microfilament Proteins; D015800:Protozoan Proteins; D012492:Salts; C101109:ctxA protein, Dictyostelium discoideum