Definition of the unfolded state of proteins is essential for understanding their stability and folding on biological timescales. Here, we find that under near physiological conditions the configurational ensemble of the unfolded state of the simplest protein structure, polyalanine alpha-helix, cannot be described by the commonly used Flory random coil model, in which configurational probabilit...

We have studied the oligomerization of an alpha-helical coiled-coil using as an example a peptide corresponding to the C-terminal domain of cartilage matrix protein. By replacing one arginine residue, which forms an interchain ionic interaction with a glutamic acid residue, with glutamine, we found that this peptide assembles into a homotetramer at neutral pH in contrast to the native molecule ...

The crystal structure at 2.0-A resolution of an 81-residue N-terminal fragment of muscle alpha-tropomyosin reveals a parallel two-stranded alpha-helical coiled-coil structure with a remarkable core. The high alanine content of the molecule is clustered into short regions where the local 2-fold symmetry is broken by a small (approximately 1.2-A) axial staggering of the helices. The joining of th...

A susceptibility gene for psoriasis, a chronic skin disorder, resides in chromosome 6p near the HLA-C locus. Sequencing of the region has allowed the identification of a new gene, HCR. We found that HCR is highly polymorphic with at least 12 coding variants. An association study of the new HCR polymorphisms and the previously suggested susceptibility alleles HLA-Cw*0602 and corneodesmosin allel...

Together with actin filaments and microtubules, intermediate filaments (IFs) are the basic cytoskeletal components of metazoan cells. Over 80 human diseases have been linked to mutations in various IF proteins to date. However, the filament structure is far from being resolved at the atomic level, which hampers rational understanding of IF pathologies. The elementary building block of all IF pr...

A theory of the helix-coil transition for in-register, two-chain, a-helical, coiled coils such as tropomyosin and paramyosin is developed. The treatment differs from those formulated previously for DNAor collagen-like double helices; in the present treatment, isolated single chains and each of the two strands in the dimer may be partially helical. We calculate the fraction of helix in the two-c...

Rod-coil molecules 1a, 1b and 2a, 2b, consisting of biphenyl and phenyl units connected by an acetylene bond as the rod segment and oligo(ethylene glycol) (OEG) as the coil segment, were synthesized and characterized. Molecules 1a and 1b incorporate a butoxy group at the apex of their bent-shaped rigid building blocks, while both 1b and 2b contain a lateral methyl group between the rod and coil...

The small GTPase Rho and one of its targets, Rho-associated kinase (ROCK), participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation. The ROCK protein consists of an N-terminal kinase domain, a central coiled-coil domain containing a Rho binding site, and a C-terminal pleckstrin homology domain. Here we present the...

The aim of this paper is to outline new possibilities of more detailed thermodynamic analysis of helix coil transition parameters, particularly with respect to their splitting into energy and entropy terms. Because of difficulties with the ternary systems, water—organic solvent polypeptide, or, two organic solvents polypeptide, caused particularly by the phenomenon of specilic sorption of one s...

Alpha helical coiled-coils appear in many important allosteric proteins such as the dynein molecular motor and bacteria chemotaxis transmembrane receptors. As a mechanism for transmitting the information of ligand binding to a distant site across an allosteric protein, an alternative to conformational change in the mean static structure is an induced change in the pattern of the internal dynami...