Ankyrin repeat proteins (ARPs) appear to be abundant in organisms from all phyla, and play critical regulatory roles, mediating specific interactions with target biomolecules and thus ordering the sequence of events in diverse cellular processes. ARPs possess a non-globular scaffold consisting of repeating motifs named ankyrin (ANK) repeats, which stack on each other. The modular architecture of ARPs provides a new paradigm for understanding protein stability and folding mechanisms. In the present study, the stability of various C-terminal fragments of the ARP p18(INK4c) was investigated by all-atomic 450 ns molecular dynamics (MD) simulations in explicit water solvent. Only motifs with at least two ANK repeats made stable systems in the available timescale. All smaller fragments were unstable, readily losing their native fold and alpha-helical content. Since each non-terminal ANK repeat has two hydrophobic sides, we may hypothesize that at least one hydrophobic side must be fully covered and shielded from the water as a necessary, but not sufficient, condition to maintain ANK repeat stability. Consequently, at least two ANK repeats are required to make a stable ARP.

Department of Physical Chemistry and Center for Biomolecules and Complex Molecular Systems Faculty of Science Palacký University tr Svobody 26 771 46 Olomouc Czech Republic

Zobrazit více v PubMed

J Mol Biol. 2007 Jan 26;365(4):1201-16 PubMed

Trends Biochem Sci. 1999 Aug;24(8):311-6 PubMed

Nature. 1993 Dec 16;366(6456):704-7 PubMed

Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1700-5 PubMed

Biochemistry. 2006 Nov 7;45(44):13131-9 PubMed

J Biol Chem. 1993 Oct 25;268(30):22703-9 PubMed

J Mol Biol. 2007 Jun 15;369(4):1015-28 PubMed

Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16029-34 PubMed

Curr Opin Struct Biol. 2005 Aug;15(4):464-71 PubMed

Nat Biotechnol. 2004 May;22(5):575-82 PubMed

Nat Struct Biol. 1998 Jan;5(1):74-81 PubMed

J Mol Biol. 2005 Dec 2;354(3):679-92 PubMed

Protein Sci. 2004 Jun;13(6):1449-57 PubMed

Protein Sci. 2005 Feb;14(2):445-51 PubMed

J Mol Biol. 2003 Sep 12;332(2):489-503 PubMed

Science. 2000 Mar 24;287(5461):2229-34 PubMed

Protein Eng. 2003 Oct;16(10):739-45 PubMed

J Mol Biol. 2007 Jan 26;365(4):1187-200 PubMed

Protein Sci. 2004 Nov;13(11):2864-70 PubMed

Biopolymers. 1983 Dec;22(12):2577-637 PubMed

J Cell Sci. 2002 Apr 15;115(Pt 8):1565-6 PubMed

J Biol Chem. 2006 Mar 17;281(11):7271-81 PubMed

J Mol Biol. 2002 Jul 5;320(2):165-70 PubMed

J Mol Biol. 2000 Jun 16;299(4):1121-32 PubMed

Proteins. 2006 Nov 1;65(2):280-4 PubMed

How ionic strength affects the conformational behavior of human and rat beta amyloids--a computational study