Molecular plasticity of β‐catenin: New insights from single‐molecule measurements and MD simulation

Ritco-Vonsovici, Monica; Ababou, Abdessamad; Horton, Michael A.

doi:10.1110/ps.072773007

Cited by 9 publications

(4 citation statements)

References 52 publications

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“…The elongated structure of SAUL1 was bent at one end due to the flexibility of the ARM repeats in the protein. This intrinsic flexibility of ARM repeats has also been described for the adenomatous polyposis coli protein and human β-catenin [12,40,41].…”

Section: Discussionmentioning

confidence: 52%

Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane

Knop

Lienemann

El-Kilani

et al. 2021

IJMS

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Plant U-box armadillo repeat (PUB-ARM) ubiquitin (Ub) ligases have important functions in plant defense through the ubiquitination of target proteins. Defense against pathogens involves vesicle trafficking and the formation of extracellular vesicles. The PUB-ARM protein SENESCENCE ASSOCIATED UBIQUITIN E3 LIGASE1 (SAUL1) can form patches at the plasma membrane related to tethering multi-vesicular bodies (MVBs) to the plasma membrane. We uncovered the structure of a full-length plant ubiquitin ligase and the structural requirements of SAUL1, which are crucial for its function in patch formation. We resolved the structure of SAUL1 monomers by small-angle X-ray scattering (SAXS). The SAUL1 model showed that SAUL1 consists of two domains: a domain containing the N-terminal U-box and armadillo (ARM) repeats and the C-terminal ARM repeat domain, which includes a positively charged groove. We showed that all C-terminal ARM repeats are essential for patch formation and that this function requires arginine residue at position 736. By applying SAXS to polydisperse SAUL1 systems, the oligomerization of SAUL1 is detectable, with SAUL1 tetramers being the most prominent oligomers at higher concentrations. The oligomerization domain consists of the N-terminal U-box and some N-terminal ARM repeats. Deleting the U-box resulted in the promotion of the SAUL1 tethering function. Our findings indicate that structural changes in SAUL1 may be fundamental to its function in forming patches at the plasma membrane.

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Section: Discussionmentioning

confidence: 52%

Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane

Knop

Lienemann

El-Kilani

et al. 2021

IJMS

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“…This multimodal distribution can be interpreted as the result of unfolding either single or multiple ARM repeats, given the number of aa contained in each ARM repeat (42 aa on average) and considering 0.4 nm as the length of a stretched aa ((27); i.e.,~17 nm/ARM repeat). Indeed, evidence for the existence of distinct conformers (i.e., molecular plasticity) in the ARM region has been already reported (35). Furthermore, the occurrence of the unfolding events was variable: we can find from two to nine force peaks in different force extension traces (with an average value of 4.5 b-catenin peaks/trace).…”

Section: Resultsmentioning

confidence: 67%

Mechanical Properties of β-Catenin Revealed by Single-Molecule Experiments

Valbuena

Vera

Oroz

et al. 2012

Biophysical Journal

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β-catenin is a central component of the adaptor complex that links cadherins to the actin cytoskeleton in adherens junctions and thus, it is a good candidate to sense and transmit mechanical forces to trigger specific changes inside the cell. To fully understand its molecular physiology, we must first investigate its mechanical role in mechanotransduction within the cadherin system. We have studied the mechanical response of β-catenin to stretching using single-molecule force spectroscopy and molecular dynamics. Unlike most proteins analyzed to date, which have a fixed mechanical unfolding pathway, the β-catenin armadillo repeat region (ARM) displays low mechanostability and multiple alternative unfolding pathways that seem to be modulated by its unstructured termini. These results are supported by steered molecular dynamics simulations, which also predict its mechanical stabilization and unfolding pathway restrictions when the contiguous α-helix of the C-terminal unstructured region is included. Furthermore, simulations of the ARM/E-cadherin cytosolic tail complex emulating the most probable stress geometry occurring in vivo show a mechanical stabilization of the interaction whose magnitude correlates with the length of the stretch of the cadherin cytosolic tail that is in contact with the ARM region.

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“…Unreacted amines were blocked with 1 m ethanolamine, pH 8.0. B0114 anti‐HSV‐1 polyclonal antibody (Dako) was dialyzed to remove the sodium azide preservative and reacted with the modified mica surface overnight as described previously and reacted with the surface similarly as described for the capsids in the previous section. Glass surface was modified by hexamethyldisilazane (HMDS, Sigma) to render it hydrophobic.…”

Section: Methodsmentioning

confidence: 99%

Photopicking: In Situ Approach for Site‐Specific Attachment of Single Multiprotein Nanoparticles to Atomic Force Microscopy Tips

Liashkovich

Rosso

Rangl

et al. 2017

Adv Funct Materials

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Ligand–receptor interactions are fundamental in life sciences and include hormone–receptor, protein–protein, pathogen–host, and cell–cell interactions, among others. Atomic force microscopy (AFM) proved to be invaluable for scrutinizing ligand–receptor interactions at the single molecular level. Basically, a ligand is attached to the AFM tip while its cognate receptor is immobilized on a surface or vice versa, and interactions are studied following triggered ligand–receptor binding. However, with rising biological complexity it becomes increasingly challenging to attach a single intact biomolecule to the tip and ensure interaction‐specific orientation. This study presents a novel strategy of inducible in situ tip functionalization with complex multiprotein nanoparticles exemplified by viral capsids, termed photopicking. It ensures a firm attachment of single 125 nm large capsids to the tip. Specific orientation is attained by weak immunosorption of capsids to the substrate and strong photoinducible covalent cross‐linking to the tip. Validation of the tip functionalization success is immediate in situ. The versatility of the strategy is further demonstrated on 20–60 nm large amino‐modified nanoparticles. In conclusion, considering the size range of the tested biomolecules, the presented strategy is applicable to viruses, viral particles, cellular organelles, multiprotein ligands/receptors, and therapeutic nanoparticles, among others. It therefore opens up exciting new avenues in broad biomedical research fields.

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Molecular plasticity of β‐catenin: New insights from single‐molecule measurements and MD simulation

Cited by 9 publications

References 52 publications

Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane

Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane

Mechanical Properties of β-Catenin Revealed by Single-Molecule Experiments

Photopicking: In Situ Approach for Site‐Specific Attachment of Single Multiprotein Nanoparticles to Atomic Force Microscopy Tips

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