scholarly journals Ambidextrous helical nanotubes from self-assembly of designed helical hairpin motifs

2019 ◽  
Vol 116 (29) ◽  
pp. 14456-14464 ◽  
Author(s):  
Spencer A. Hughes ◽  
Fengbin Wang ◽  
Shengyuan Wang ◽  
Mark A. B. Kreutzberger ◽  
Tomasz Osinski ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Self Assembly ◽  
Sequence Similarity ◽  
Structural Data ◽  
Consensus Sequences ◽  
Repeat Proteins ◽  
Helical Hairpin ◽  
Tandem Repeat Proteins ◽  
Helical Protein ◽  
Helical Geometry

Tandem repeat proteins exhibit native designability and represent potentially useful scaffolds for the construction of synthetic biomimetic assemblies. We have designed 2 synthetic peptides, HEAT_R1 and LRV_M3Δ1, based on the consensus sequences of single repeats of thermophilic HEAT (PBS_HEAT) and Leucine-Rich Variant (LRV) structural motifs, respectively. Self-assembly of the peptides afforded high-aspect ratio helical nanotubes. Cryo-electron microscopy with direct electron detection was employed to analyze the structures of the solvated filaments. The 3D reconstructions from the cryo-EM maps led to atomic models for the HEAT_R1 and LRV_M3Δ1 filaments at resolutions of 6.0 and 4.4 Å, respectively. Surprisingly, despite sequence similarity at the lateral packing interface, HEAT_R1 and LRV_M3Δ1 filaments adopt the opposite helical hand and differ significantly in helical geometry, while retaining a local conformation similar to previously characterized repeat proteins of the same class. The differences in the 2 filaments could be rationalized on the basis of differences in cohesive interactions at the lateral and axial interfaces. These structural data reinforce previous observations regarding the structural plasticity of helical protein assemblies and the need for high-resolution structural analysis. Despite these observations, the native designability of tandem repeat proteins offers the opportunity to engineer novel helical nanotubes. Moreover, the resultant nanotubes have independently addressable and chemically distinguishable interior and exterior surfaces that would facilitate applications in selective recognition, transport, and release.

scholarly journals Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jazmine P. Hallinan ◽  
Lindsey A. Doyle ◽  
Betty W. Shen ◽  
Mesfin M. Gewe ◽  
Brittany Takushi ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Self Assembly ◽  
De Novo ◽  
Viral Receptor ◽  
Viral Neutralization ◽  
Sh2 Domains ◽  
Repeat Proteins ◽  
Wide Range ◽  
Tandem Repeat Proteins ◽  
New Generation

AbstractCircular tandem repeat proteins (‘cTRPs’) are de novo designed protein scaffolds (in this and prior studies, based on antiparallel two-helix bundles) that contain repeated protein sequences and structural motifs and form closed circular structures. They can display significant stability and solubility, a wide range of sizes, and are useful as protein display particles for biotechnology applications. However, cTRPs also demonstrate inefficient self-assembly from smaller subunits. In this study, we describe a new generation of cTRPs, with longer repeats and increased interaction surfaces, which enhanced the self-assembly of two significantly different sizes of homotrimeric constructs. Finally, we demonstrated functionalization of these constructs with (1) a hexameric array of peptide-binding SH2 domains, and (2) a trimeric array of anti-SARS CoV-2 VHH domains. The latter proved capable of sub-nanomolar binding affinities towards the viral receptor binding domain and potent viral neutralization function.

scholarly journals Identification of new silk-like protein from B. magister and development of functional materials based on it

2021 ◽  
Vol 2086 (1) ◽  
pp. 012123
Author(s):  
A A Vronskaia ◽  
A D Mikushina ◽  
I E Eliseev
Keyword(s):  
Thin Films ◽  
Drug Delivery ◽  
Tandem Repeat ◽  
Composite Structure ◽  
Textile Industry ◽  
Functional Materials ◽  
Repeat Proteins ◽  
Tandem Repeat Proteins ◽  
New Protein

Abstract Tandem repeat proteins have composite structure and unique properties, which allow them to be used in multiple fields, such as soft photonics, drug delivery and textile industry. The recent discovery of squid ring teeth (SRT) proteins have expanded the existing repertoire of repetitive polypeptides. We chose previously unexplored squid B. magister for our research, isolated and analyzed a new protein forming its ring teeth and hooks, and amplified the corresponding gene. Finally, we used this new isolated SRT protein to fabricate transparent thin films and microspheres.

Mechanical Properties of Tandem-Repeat Proteins Are Governed by Network Defects

2018 ◽  
Vol 4 (3) ◽  
pp. 884-891 ◽  
Author(s):  
Abdon Pena-Francesch ◽  
Huihun Jung ◽  
Mo Segad ◽  
Ralph H. Colby ◽  
Benjamin D. Allen ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Tandem Repeat ◽  
Repeat Proteins ◽  
Tandem Repeat Proteins

scholarly journals Dissecting and reprogramming the folding and assembly of tandem-repeat proteins

2015 ◽  
Vol 43 (5) ◽  
pp. 881-888 ◽  
Author(s):  
Pamela J.E. Rowling ◽  
Elin M. Sivertsson ◽  
Albert Perez-Riba ◽  
Ewan R.G. Main ◽  
Laura S. Itzhaki
Keyword(s):  
Protein Design ◽  
Tandem Repeat ◽  
Rational Design ◽  
Topological Complexity ◽  
Energy Barriers ◽  
Step Size ◽  
Repeat Proteins ◽  
Tandem Repeat Proteins ◽  
Level Of Understanding ◽  
Modular Structures

Studying protein folding and protein design in globular proteins presents significant challenges because of the two related features, topological complexity and co-operativity. In contrast, tandem-repeat proteins have regular and modular structures composed of linearly arrayed motifs. This means that the biophysics of even giant repeat proteins is highly amenable to dissection and to rational design. Here we discuss what has been learnt about the folding mechanisms of tandem-repeat proteins. The defining features that have emerged are: (i) accessibility of multiple distinct routes between denatured and native states, both at equilibrium and under kinetic conditions; (ii) different routes are favoured for folding compared with unfolding; (iii) unfolding energy barriers are broad, reflecting stepwise unravelling of an array repeat by repeat; (iv) highly co-operative unfolding at equilibrium and the potential for exceptionally high thermodynamic stabilities by introducing consensus residues; (v) under force, helical-repeat structures are very weak with non-co-operative unfolding leading to elasticity and buffering effects. This level of understanding should enable us to create repeat proteins with made-to-measure folding mechanisms, in which one can dial into the sequence the order of repeat folding, number of pathways taken, step size (co-operativity) and fine-structure of the kinetic energy barriers.

scholarly journals DeepSymmetry: using 3D convolutional networks for identification of tandem repeats and internal symmetries in protein structures

2019 ◽  
Vol 35 (24) ◽  
pp. 5113-5120 ◽  
Author(s):  
Guillaume Pagès ◽  
Sergei Grudinin
Keyword(s):  
Tandem Repeat ◽  
Tandem Repeats ◽  
Protein Structures ◽  
Molecular Structures ◽  
Supplementary Information ◽  
Convolutional Networks ◽  
Repeat Proteins ◽  
Density Maps ◽  
Tandem Repeat Proteins ◽  
Internal Symmetries

Abstract Motivation Thanks to the recent advances in structural biology, nowadays 3D structures of various proteins are solved on a routine basis. A large portion of these structures contain structural repetitions or internal symmetries. To understand the evolution mechanisms of these proteins and how structural repetitions affect the protein function, we need to be able to detect such proteins very robustly. As deep learning is particularly suited to deal with spatially organized data, we applied it to the detection of proteins with structural repetitions. Results We present DeepSymmetry, a versatile method based on 3D convolutional networks that detects structural repetitions in proteins and their density maps. Our method is designed to identify tandem repeat proteins, proteins with internal symmetries, symmetries in the raw density maps, their symmetry order and also the corresponding symmetry axes. Detection of symmetry axes is based on learning 6D Veronese mappings of 3D vectors, and the median angular error of axis determination is less than one degree. We demonstrate the capabilities of our method on benchmarks with tandem-repeated proteins and also with symmetrical assemblies. For example, we have discovered about 7800 putative tandem repeat proteins in the PDB. Availability and implementation The method is available at https://team.inria.fr/nano-d/software/deepsymmetry. It consists of a C++ executable that transforms molecular structures into volumetric density maps, and a Python code based on the TensorFlow framework for applying the DeepSymmetry model to these maps. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Upregulated Expression of B-Cell Antigen Family Tandem Repeat Proteins by Leishmania Amastigotes

2010 ◽  
Vol 78 (5) ◽  
pp. 2138-2145 ◽  
Author(s):  
Yasuyuki Goto ◽  
Darrick Carter ◽  
Jeffrey Guderian ◽  
Noboru Inoue ◽  
Shin-Ichiro Kawazu ◽  
...  
Keyword(s):  
B Cell ◽  
Tandem Repeat ◽  
Transmembrane Domain ◽  
Signal Sequence ◽  
Sequence Similarity ◽  
Factors Affecting ◽  
Antigenic Proteins ◽  
Trypanosomatid Parasites ◽  
Tandem Repeat Proteins ◽  
Leishmania Amastigotes

ABSTRACT Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, and they are often targets of B-cell responses. Through systematic analyses of whole proteomes, we recently demonstrated that two trypanosomatid parasites, Leishmania infantum and Trypanosoma cruzi, are rich in antigenic proteins with large TR domains. However, the reason that these proteins are antigenic was unclear. Here, by performing molecular, immunological, and bioinformatic characterizations of Leishmania TR proteins, we found two possible factors affecting the antigenicity of these proteins; one factor is their fundamental composition as TR proteins, and the other is regulation of their expression by parasites. Enzyme-linked immunosorbent assays (ELISAs) using recombinant proteins revealed that the copy number of the repeat affects the affinity of binding between antigens and antibodies, as expected based on thermodynamic binding kinetics. Other than containing TR domains, the TR proteins do not share characteristics, such as sequence similarity or biased cellular location predicted by the presence of a signal sequence(s) and/or a transmembrane domain(s). However, the TR proteome contained a higher percentage of proteins upregulated in amastigotes than the whole proteome, and upregulated expression of a TR protein seemed to affect its antigenicity. These results indicate that Leishmania parasites actively utilize the TR protein family for parasitism in mammalian hosts.

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