An interdomain bridge influences RNA binding of the human La protein

Marrella, Stefano A; Brown, Kerene A.; Mansouri-Noori, Farnaz; Porat, Jennifer; Wilson, Derek J.; Bayfield, Mark A.

doi:10.1074/jbc.ra118.003995

Cited by 10 publications

(6 citation statements)

References 43 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRESI-HDX-MS is similar to classical “bottom up” hydrogen–deuterium exchange experiments but uses millisecond–low second labeling times. This approach allows for the characterization of weakly ordered conformational ensembles, including IDPs. ,, It has been applied in a wide range of systems involving rapid conformational changes including protein-RNA/DNA , and lipid interaction, enzymatic transition states, intrinsically disordered protein folding/misfolding intermediates, and antibody–antigen interactions. , …”

Section: Introductionmentioning

confidence: 99%

“…This approach allows for the characterization of weakly ordered conformational ensembles, including IDPs. 38,61,62 It has been applied in a wide range of systems involving rapid conformational changes including protein-RNA/DNA 63,64 and lipid interaction, 65 enzymatic transition states, 66 intrinsically disordered protein folding/misfolding intermediates, 67 and antibody−antigen interactions. 68,69 In the TRESI-HDX setup used in the current study, millisecond hydrogen−deuterium exchange reaction times are made possible by a concentric capillary rapid mixer labeled as "HDX reaction chamber" in Figure 1.…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conformational Dynamics of α-Synuclein during the Interaction with Phospholipid Nanodiscs by Millisecond Hydrogen–Deuterium Exchange Mass Spectrometry

Oganesyan

Lento

Tandon

et al. 2021

J. Am. Soc. Mass Spectrom.

Self Cite

View full text Add to dashboard Cite

Both normal and pathological functions of αsynuclein (αSN), an abundant protein in the central and peripheral nervous system, have been linked to its interaction with membrane lipid bilayers. The ability to characterize structural transitions of αSN upon membrane complexation will clarify molecular mechanisms associated with αSN-linked pathologies, including Parkinson's disease (PD), multiple systems atrophy, and other synucleinopathies. In this work, time-resolved electrospray ionization hydrogen/deuterium exchange mass spectrometry (TRESI-HDX-MS) was employed to acquire a detailed picture of αSN's conformational transitions as it undergoes complexation with nanodisc membrane mimics with different headgroup charges (zwitterionic DMPC and negative POPG). Using this approach, αSN interactions with DMPC nanodiscs were shown to be rapid exchanging and to have little impact on the αSN conformational ensemble. Interactions with nanodiscs containing lipids known to promote amyloidogenesis (e.g., POPG), on the other hand, were observed to induce substantial and specific changes in the αSN conformational ensemble. Ultimately, we identify a region corresponding residues 19−28 and 45−57 of the αSN sequence that is uniquely impacted by interactions with "amyloidogenic" lipid membranes, supporting the existing "broken-helix" model for αsynuclein/membrane interactions, but do not detect a "helical extension" that is also thought to play a role in αSN aggregation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Conformational Dynamics of α-Synuclein during the Interaction with Phospholipid Nanodiscs by Millisecond Hydrogen–Deuterium Exchange Mass Spectrometry

Oganesyan

Lento

Tandon

et al. 2021

J. Am. Soc. Mass Spectrom.

Self Cite

View full text Add to dashboard Cite

show abstract

“…There have been sufficient studies to prove the RNA chaperone function of La protein, which is involved in all aspects of RNA metabolism. The biological function of La protein is based on its RNA-binding function ( 40 ). Therefore, it is suggested that La protein may play its RNA chaperone function by binding to the mRNA of the above 11 genes, regulating RNA transcription, translation, or stability, and further affecting protein expression.…”

Section: Discussionmentioning

confidence: 99%

La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer

Huang

Zhu

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Research on the mechanism and new targets of ovarian cancer is of great significance to reduce the high mortality and drug resistance of ovarian cancer. Human La protein has been found to be highly expressed in a variety of malignant tumors and plays a role in tumorigenesis and development through its RNA-binding function. However, its role and mechanism in ovarian cancer are not completely clear. The present study showed that La protein was highly expressed in serum and tissues of patients with ovarian cancer by ELISA and immunohistochemistry, and the high expression of La protein was associated with the increased degree of malignancy and poor prognosis by searching the KM plotter database. Interference of the La gene resulted in a significant decrease in the proliferation, migration, and invasion of ovarian cancer cells with growth block in the G1 phase and increasing apoptosis. By RNA binding protein immunoprecipitation, transcriptome sequencing, and proteomics, 14 downstream target genes were screened. The La protein might affect the protein expression of these 14 genes by binding with the mRNAs. Therefore, it played a role in the pathological process of ovarian cancer.

show abstract

“…This work revealed that lcn2 underwent substantial conformational distortion in order to accommodate enterobactin, suggesting that lcn2’s physiological role as a siderophore scavenger may represent an example of molecular exaptation (where a protein that evolved for one role is recruited for another in the course of evolution) . A pair of studies in 2016 and 2019 by Brown and co-workers used subsecond time-resolved HDX and IMS/CIU to explore the interaction between the human La protein (and RNA chaperone) and its varied RNA targets. , In addition to providing biological insights into the dynamics underlying ligand selectivity in human La, the former study also included a direct comparison between a bottom-up HDX analysis and an NMR chemical shift perturbation assay, showing a moderate degree of correlation between these two probes of ligand binding . The latter study combined subsecond time-resolved HDX, collision-induced unfolding (an ion mobility-based technique), and mutational analysis for a detailed examination of interdomain conformation and dynamics in human La during ligand binding, confirming the occurrence of a transient, interdomain bridge that controlled specificity and cooperativity in RNA binding …”

Section: Time-resolved Ms In Protein Dynamicsmentioning

confidence: 99%

Subsecond Time-Resolved Mass Spectrometry in Dynamic Structural Biology

Lento

Wilson

2021

Chem. Rev.

Self Cite

View full text Add to dashboard Cite

Life at the molecular level is a dynamic world, where the key playersproteins, oligonucleotides, lipids, and carbohydratesare in a perpetual state of structural flux, shifting rapidly between local minima on their conformational free energy landscapes. The techniques of classical structural biology, X-ray crystallography, structural NMR, and cryo-electron microscopy (cryo-EM), while capable of extraordinary structural resolution, are innately ill-suited to characterize biomolecules in their dynamically active states. Subsecond time-resolved mass spectrometry (MS) provides a unique window into the dynamic world of biological macromolecules, offering the capacity to directly monitor biochemical processes and conformational shifts with a structural dimension provided by the electrospray charge-state distribution, ion mobility, covalent labeling, or hydrogen–deuterium exchange. Over the past two decades, this suite of techniques has provided important insights into the inherently dynamic processes that drive function and pathogenesis in biological macromolecules, including (mis)folding, complexation, aggregation, ligand binding, and enzyme catalysis, among others. This Review provides a comprehensive account of subsecond time-resolved MS and the advances it has enabled in dynamic structural biology, with an emphasis on insights into the dynamic drivers of protein function.

show abstract

An interdomain bridge influences RNA binding of the human La protein

Cited by 10 publications

References 43 publications

Conformational Dynamics of α-Synuclein during the Interaction with Phospholipid Nanodiscs by Millisecond Hydrogen–Deuterium Exchange Mass Spectrometry

Conformational Dynamics of α-Synuclein during the Interaction with Phospholipid Nanodiscs by Millisecond Hydrogen–Deuterium Exchange Mass Spectrometry

La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer

Subsecond Time-Resolved Mass Spectrometry in Dynamic Structural Biology

Contact Info

Product

Resources

About