Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine. However, the inability to target MSCs in tissues of interest with high efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in ...

The analysis of conformations corresponding to continuous amino acid repeat peptides (CARPs) comprising six or more residues in proteins of known three-dimensional structure revealed that alanine, glycine, glutamic acid, proline, valine, histidine, aspartic acid, glutamine and lysine were associated as repeating amino acid residues. Alanine, glycine and histidine CARPs were ...

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 ...

NadA is a trimeric autotransporter protein of Neisseria meningitidis belonging to the group of oligomeric coiled-coil adhesins. It is implicated in the colonization of the human upper respiratory tract by hypervirulent serogroup B N. meningitidis strains and is part of a multiantigen anti-serogroup B vaccine. Structure prediction indicates that NadA ...

The first computationally designed self-assembling oligomer consisting of exclusively β-amino acids (βAAs) is presented. The packing of a β-3(14) helix into coiled-coils of varying stoichiometries as a function of amino acid sequence is examined. β-Peptides with hVal repeating every third residue in the sequence appeared to have a strong propensity ...

Tetherin/BST2 is a type-II membrane protein that inhibits the release of a range of enveloped viruses, including HIV-1. Here we report three crystal structures of human tetherin, including the full-length ectodomain, a triple cysteine mutant and an ectodomain truncation. These structures show that tetherin forms a continuous alpha helix encompassing ...

AQ-Pal14 is a 30-residue polypeptide that was designed to form an α-helical coiled coil that contains a metal-binding 4-pyridylalanine residue on its solvent-exposed surface. However, characterization of this peptide shows that it exists as a three-stranded coiled coil, not a two-stranded one as predicted from its design. Reaction with cobalt(III) ...

Because the space of folded protein structures is highly degenerate, with recurring secondary and tertiary motifs, methods for representing protein structure in terms of collective physically relevant coordinates are of great interest. By collapsing structural diversity to a handful of parameters, such methods can be used to delineate the space ...

Stomatin is a major integral membrane protein of human erythrocytes, the absence of which is associated with a form of hemolytic anemia known as hereditary stomatocytosis. It is reported that stomatin regulates the gating of acid-sensing ion channels in mammalian neurons. However, the function of stomatin is not fully understood. ...

HIV-1 and other enveloped viruses can be restricted by a host cellular protein called BST2/tetherin that prevents release of budded viruses from the cell surface. Mature BST2 contains a small cytosolic region, a predicted transmembrane helix, and an extracellular domain with a C-terminal GPI anchor. To advance understanding of BST2 ...

Gas vesicles are gas-filled buoyancy organelles with walls that consist almost exclusively of gas vesicle protein A (GvpA). Intact, collapsed gas vesicles from the cyanobacterium Anabaena flos-aquae were studied by solid-state NMR spectroscopy, and most of the GvpA sequence was assigned. Chemical shift analysis indicates a coil-α-β-β-α-coil peptide backbone, consistent ...

S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one of the molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed the site of S-nitrosylation in 328 peptides in 192 proteins endogenously modified in WT mouse ...

We have determined the 2.2-Å structure of the HP0958 protein from the human gastric pathogen Helicobacter pylori. HP0958 is essential for flagellum formation and motility. It functions as a chaperone for RpoN (σ(54)) and also controls the stability and translation of mRNA for the major flagellin subunit FlaA. The protein ...

Prostate apoptosis response factor-4 (Par-4) is a pro-apoptotic and tumor-suppressive protein. A highly conserved heptad repeat sequence at the Par-4 C-terminus suggests the presence of a leucine zipper (LZ). This C-terminal region is essential for Par-4 self-association and interaction with various effector proteins. We have used nuclear magnetic resonance (NMR) ...

Self-assembly has been increasingly utilized in recent years to create peptide-based biomaterials for 3D cell culture, tissue engineering, and regenerative medicine, but the molecular determinants of these materials' immunogenicity have remained largely unexplored. In this study, a set of molecules that self-assembled through coiled coil oligomerization was designed and synthesized, ...

The mechanism of polypeptide folding, especially for the formation of tertiary structures, within the ribosomal exit tunnel, remains one of the most important unsolved problems in biophysical chemistry and molecular biology. In this work, we use a density functional theory (DFT) to explore the polypeptide folding within a modified nanopore, ...

The tetratricopeptide repeat (TPR) motif is a protein-protein interaction module that acts as an organizing centre for complexes regulating a multitude of biological processes. Despite accumulating evidence for the formation of TPR oligomers as an additional level of regulation there is a lack of structural and solution data explaining TPR ...

A quantitative analysis of the direction of bending of two-stranded alpha-helical coiled coils in crystal structures has been carried out to help determine how the amino acid sequence of the coiled coil influences its shape and function. Change in the axial staggering of the coiled coil, occurring at the boundaries ...

Tropomyosin is a stereotypical alpha-helical coiled coil that polymerizes to form a filamentous macromolecular assembly that lies on the surface of F-actin. The interaction between the C-terminal and N-terminal segments on adjacent molecules is known as the overlap region. We report here two X-ray structures of the chicken smooth muscle ...

Amphiphilic peptide-polymer conjugates can lead to hierarchically structured, biomolecular materials. Because the peptide structure determines the size, shape, and intermolecular interactions of these building blocks, systematic understanding of how the peptide structure and functionality are affected upon implementing hydrophobicity is required to direct their assemblies in solution and in the ...

Hpa1(Xoo) (harpin) is a type III secreted protein of the rice blight bacterial pathogen Xanthomonas oryzae pv. oryzae that elicits a hypersensitive response (HR) in nonhost tobacco. Hpa1(Xoo) is predicted to contain two potential coiled-coil (CC) regions, one at the N-terminus with a high probability of formation, and one at ...

A new strategy for rapid evaluation of sequence-stability relationships in the parallel coiled-coil motif is described. The experimental design relies upon thiol-thioester exchange equilibria, an approach that is particularly well suited to examination of heterodimeric systems. Our model system has been benchmarked by demonstrating that it can quantitatively reproduce previously ...

In view of the important role helix-sheet transitions play in protein aggregation, we introduce a simple model to study secondary structural transitions of helix-coil-sheet systems using a Potts model starting with an effective Hamiltonian. This energy function depends on four parameters that approximately describe entropic and enthalpic contributions to the ...

The combination of peptide molecular recognition and residue-selective dirhodium catalysis allows modification of aromatic side chains that is selective for coil structures. A rate enhancement of >10(3) relative to nonselective dirhodium modification was observed. The increased reactivity of this approach creates the first selective chemical modification of the phenylalanine residue.

This article reports the design, synthesis and results of first in vitro model studies of a conceptually novel class of polymer therapeutics in which the cargo is attached to a polymer backbone via a noncovalent, biologically inspired coiled coil linker, which is formed by heterodimerization of two complementary peptide sequences ...

The versatile coiled-coil protein motif is widely used to induce and control macromolecular interactions in biology and materials science. Yet the types of interaction patterns that can be constructed using known coiled coils are limited. Here we greatly expand the coiled-coil toolkit by measuring the complete pairwise interactions of 48 ...

The restriction factor BST-2/tetherin contains two membrane anchors employed to retain some enveloped viruses, including HIV-1 tethered to the plasma membrane in the absence of virus-encoded antagonists. The 2.77 A crystal structure of the BST-2/tetherin extracellular core presented here reveals a parallel 90 A long disulfide-linked coiled-coil domain, while the ...

3-(trifluoromethyl)bicyclopent-[1.1.1]-1-yl glycine (CF3-Bpg) has previously been established as a useful 19F NMR label to analyse the structures of oligomeric membrane-active peptides or transmembrane segments. To systematically examine the effect of side chain volume, conformational rigidity, and hydrophobicity of CF3-Bpg in polypeptide environments the amino acid was incorporated into an established ...

Complete amino acid sequences of the four major proteins (Vssilk 1-4) of silk (hornet silk) obtained from yellow hornet ( Vespa simillima , Vespinae, Vespidae) cocoons have been determined. The native structure of the hornet silk (HS), in which Vssilk 1-4 have an alpha-helix domain with coiled-coil alpha-helices and a ...

Biological self-assembly is very complex and results in highly functional materials. In effect, it takes a bottom-up approach using biomolecular building blocks of precisely defined shape, size, hydrophobicity, and spatial distribution of functionality. Inspired by, and drawing lessons from self-assembly processes in nature, scientists are learning how to control the ...

Nuclear pore complexes (NPCs) gate the only conduits for nucleocytoplasmic transport in eukaryotes. Their gate is formed by nucleoporins containing large intrinsically disordered domains with multiple phenylalanine-glycine repeats (FG domains). In combination, these are hypothesized to form a structurally and chemically homogeneous network of random coils at the NPC center, ...

A strategy has been demonstrated that utilizes a phosphatase as a natural tool for the triggering and control of amyloid formation in a coiled coil peptide model under conditions that closely approximate a physiological environment.

Secondary structure transitions are important modulators of signal transduction and protein aggregation. Phosphorylation is a well known post-translational modification capable of dramatic alteration of protein secondary structure. Additionally, phosphorylated residues can induce structural changes through metal binding. Data derived from the Protein Data Bank demonstrate that magnesium and manganese are ...

The aim of this study was to investigate the influence of multiple O-glycosylation in alpha-helical coiled coil peptides on the folding and stability. For this purpose we systematically incorporated one to six beta-galactose residues into the solvent exposed positions of a 26 amino acid long coiled coil helix. Surprisingly, circular ...

As the smallest and simplest motor enzymes, kinesins have served as the prototype for understanding the relationship between protein structure and mechanochemical function of enzymes in this class. Conventional kinesin (kinesin-1) is a motor enzyme that transports cargo toward the plus end of microtubules by a processive, asymmetric hand-over-hand mechanism. ...

Coiled coils represent the most frequent protein oligomerization motif in nature and are involved in many important biological processes. The prototype interhelical ionic interaction for coiled coils described in literature is an i to i+5 ionic interaction from heptad position g to e', but other possible ionic interactions have also ...

A new class of peptide has been created, polypeptide-b-designed peptides, which unites the useful qualities of the two constituent peptide types. We demonstrate the synthesis and self-assembly possibilities of this class of peptide chimera with a series of amphiphilic polypeptide-b-designed peptides in which the hydrophobic block is poly(gamma-benzyl l-glutamate) (PBLG) ...

Trimeric autotransporter adhesins (TAAs) represent an important class of pathogenicity factors in proteobacteria. Their defining feature is a conserved membrane anchor, which forms a 12-stranded beta-barrel through the outer membrane. The proteins are translocated through the pore of this barrel and, once export is complete, the pore is occluded by ...

Intermediate filaments (IFs) are essential cytoskeletal components in metazoan cells. They assemble from elementary dimers that are built around the central alpha-helical coiled-coil rod domain representing the IF 'signature'. The rod consists of two similarly-sized parts, coil 1 and coil 2, connected by a non-alpha-helical linker L12. Coil 2 is ...

Anhydrobiotic (i.e., life without water) organisms are known to produce group 3 late embryogenesis abundant (G3LEA) proteins during adaptation to severely water-deficient conditions. Their primary amino acid sequences are composed largely of loosely conserved 11-mer repeat units. However, little information has been obtained for the structural and functional roles of ...

Laminins are large heterotrimeric, multidomain proteins that play a central role in organising and establishing all basement membranes. Despite a total of 45 potential heterotrimeric chain combinations formed through the coiled-coil domain of the 11 identified laminin chains (alpha1-5, beta1-3, gamma1-3), to date only 15 different laminin isoforms have been ...

Our laboratory has recently described a stability control region in the two-stranded alpha-helical coiled-coil alpha-tropomyosin that accounts for overall protein stability but is not required for folding (Hodges et al., 2009). We have used a synthetic peptide approach to investigate three stability control sites within the stability control region (residues ...

As the microtubule-organizing center of yeast, the spindle pole body (SPB) is essential for cell viability. Structural studies of the SPB are limited by its low copy number in the cell, its large size and heterogeneous composition, and its association with the nuclear membrane. However, low-resolution or indirect structural information ...

Four-helical bundles are the most abundant topological motif among helical folds. Their constituent helices show crossing angles that mainly cluster around +20 degrees (aligned) or -50 degrees (orthogonal). Bundles with all helices aligned are called 'square' and comprise four-helical coiled coils as their structurally most regular form. Since coiled coils ...

Coiled coil is a ubiquitous structural motif in proteins, with two to seven alpha helices coiled together like the strands of a rope, and coiled coil folding and assembly is not completely understood. A GCN4 leucine zipper mutant with four mutations of K3A, D7A, Y17W, and H18N has been designed, ...

Over the decade and a half, interest has soared in the development of peptide-based biomaterials and their potential applications in biotechnology. This review outlines the advances during this time in the construction of biomaterials based on the alpha-helical coiled-coil and collagen-like peptides. These structures and the resulting designs are distinct ...

This review presents an overview on bio-hybrid approaches of integrating the structural and functional features of proteins and peptides with synthetic polymers and the resulting unique properties in such hybrids, with a focus on bioresponsive/bioactive systems with biomaterials applications. The review is divided in two broad sections. First, we describe ...

BACKGROUND: Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are two categories of E. coli strains associated with human disease. A major virulence factor of both pathotypes is the expression of a type three secretion system (TTSS), responsible for their ability to adhere to gut mucosa causing a characteristic ...

The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, Anopheles gambiae, has uncovered an array of components and mechanisms involved in defence against ...

Complementarity between the tropomyosin supercoil and the helical contour of actin-filaments is required for the binding interaction of actin and tropomyosin (Li et al., 2010). Clusters of small alanine residues in place of canonical leucines along coiled-coil tropomyosin may be responsible for pre-shaping tropomyosin and promoting conformational complementarity to F-actin. ...