Molecular basis of coiled-coil oligomerization-state specificity
- 2 November 2010
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (46), 19850-19855
- https://doi.org/10.1073/pnas.1008502107
Abstract
Coiled coils are extensively and successfully used nowadays to rationally design multistranded structures for applications, including basic research, biotechnology, nanotechnology, materials science, and medicine. The wide range of applications as well as the important functions these structures play in almost all biological processes highlight the need for a detailed understanding of the factors that control coiled-coil folding and oligomerization. Here, we address the important and unresolved question why the presence of particular oligomerization-state determinants within a coiled coil does frequently not correlate with its topology. We found an unexpected, general link between coiled-coil oligomerization-state specificity and trigger sequences, elements that are indispensable for coiled-coil formation. By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we show that well-established trimer-specific oligomerization-state determinants switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence. We successfully confirmed our results in two other, unrelated coiled-coil dimers, ATF1 and cortexillin-1. We furthermore show that multiple topology determinants can coexist in the same trigger sequence, revealing a delicate balance of the resulting oligomerization state by position-dependent forces. Our experimental results should significantly improve the prediction of the oligomerization state of coiled coils. They therefore should have major implications for the rational design of coiled coils and consequently many applications using these popular oligomerization domains.Keywords
This publication has 19 references indexed in Scilit:
- Crystal structure of a trimeric form of the KV7.1 (KCNQ1) A‐domain tail coiled‐coil reveals structural plasticity and context dependent changes in a putative coiled‐coil trimerization motifProtein Science, 2009
- A conserved tyrosine in the neck of a fungal kinesin regulates the catalytic motor coreThe EMBO Journal, 2003
- The Structure of a CREB bZIP·Somatostatin CRE Complex Reveals the Basis for Selective Dimerization and Divalent Cation-enhanced DNA BindingPublished by Elsevier BV ,2000
- The coiled-coil trigger site of the rod domain of cortexillin I unveils a distinct network of interhelical and intrahelical salt bridgesStructure, 2000
- An autonomous folding unit mediates the assembly of two-stranded coiled coilsProceedings of the National Academy of Sciences of the United States of America, 1998
- Sequence-based design of a peptide probe for the APC tumor suppressor proteinCurrent Biology, 1998
- A distinct 14 residue site triggers coiled-coil formation in cortexillin IThe EMBO Journal, 1998
- Crystal structure of an isoleucine-zipper trimerNature, 1994
- A Switch Between Two-, Three-, and Four-stranded Coiled Coils in GCN4 Leucine Zipper MutantsScience, 1993
- X-Ray Structure of the GCN4 Leucine Zipper, a Two-Stranded, Parallel Coiled CoilScience, 1991