Functions of intrinsic disorder in transmembrane proteins

Kjærgaard, Magnus; Kragelund, Birthe B.

doi:10.1007/s00018-017-2562-5

Cited by 68 publications

(47 citation statements)

References 213 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the growing availability of structural information (as in 34,89 ) can be used to guide mutational analyses and interpretations about phosphorylation in well-ordered protein domains. In addition, the recognition that intrinsically disordered protein domains are enriched in phosphorylation 101 and are particularly important in trafficking and protein localization 102 is highly relevant. The cytoplasmic domains of cldns and JAM-A, as well as regions within the ocln tail are predicted to be disordered by several algorithms; 103,104 phosphorylation in these regions has different implications than that in highly structured domains.…”

Section: Future Approachesmentioning

confidence: 99%

Phosphorylation of tight junction transmembrane proteins: Many sites, much to do

Itallie

Anderson

2017

Tissue Barriers

View full text Add to dashboard Cite

Phosphorylation is a dynamic post-translational modification that can alter protein structure, localization, protein-protein interactions and stability. All of the identified tight junction transmembrane proteins can be multiply phosphorylated, but only in a few cases are the consequences of phosphorylation at specific sites well characterized. The goal of this review is to highlight some of the best understood examples of phosphorylation changes in the integral membrane tight junction proteins in the context of more general overview of the effects of phosphorylation throughout the proteome. We expect as that structural information for the tight junction proteins becomes more widely available and the molecular modeling algorithms improve, so will our understanding of the relevance of phosphorylation changes at single and multiple sites in tight junction proteins.

show abstract

Section: Future Approachesmentioning

confidence: 99%

Phosphorylation of tight junction transmembrane proteins: Many sites, much to do

Itallie

Anderson

2017

Tissue Barriers

View full text Add to dashboard Cite

show abstract

“…Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) comprise up to 40% of the proteomes in all life forms (1). They are involved in numerous cellular functions including regulation and signaling (2,3). As such, dysregulation, misfolding, and aggregation of IDPs lead to many diseases (4,5).…”

Section: Introductionmentioning

confidence: 99%

Sequence-dependent correlated segments in the intrinsically disordered region of ChiZ

Hicks

Escobar

Cross

et al. 2020

Preprint

View full text Add to dashboard Cite

Intrinsically disordered proteins (IDPs) account for a significant fraction of any proteome and are central to numerous cellular functions. Yet how sequences of IDPs code for their conformational dynamics is poorly understood. Here we combined NMR spectroscopy, small-angle X-ray scattering (SAXS), and molecular dynamics (MD) simulations to characterize the conformations and dynamics of ChiZ1-64. This IDP is the N-terminal fragment (residues 1-64) of the transmembrane protein ChiZ, a component of the cell division machinery in Mycobacterium tuberculosis. Its Nhalf contains most of the prolines and all of the anionic residues while the C-half most of the glycines and cationic residues. MD simulations, first validated by SAXS and secondary chemical shift data, found scant a-helices or b-strands but considerable propensity for polyproline II (PPII) torsion angles. Importantly, several blocks of residues (e.g., 11-29) emerge as "correlated segments", identified by frequent formation of PPII stretches, salt bridges, cation-p interactions, and sidechain-backbone hydrogen bonds. NMR relaxation experiments showed non-uniform transverse relaxation rates (R2s) and nuclear Overhauser enhancements (NOEs) along the sequence (e.g., high R2s and NOEs for residues 11-14 and 23-28). MD simulations further revealed that the extent of segmental correlation is sequence-dependent: segments where internal interactions are more prevalent manifest elevated "collective" motions on the 5-10 ns timescale and suppressed local motions on the sub-ns timescale. Amide proton exchange rates provides corroboration, with residues in the most correlated segment exhibiting the highest protection factors. We propose correlated segment as a defining feature for the conformation and dynamics of IDPs.

show abstract

“…In the context of protein-related diseases, unraveling them is fundamental in order to better understand both the amyloid formation in vivo and the related toxicity [30]. To this aim a great attention has been recently addressed to the interaction between intrinsically disordered regions of proteins and membrane, which may be involved both in protein function and dysfunction in cellular environment [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Direct observation of alpha-lactalbumin, adsorption and incorporation into lipid membrane and formation of lipid/protein hybrid structures

Rao

Foderà

Leone

et al. 2019

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Functions of intrinsic disorder in transmembrane proteins

Cited by 68 publications

References 213 publications

Phosphorylation of tight junction transmembrane proteins: Many sites, much to do

Phosphorylation of tight junction transmembrane proteins: Many sites, much to do

Sequence-dependent correlated segments in the intrinsically disordered region of ChiZ

Direct observation of alpha-lactalbumin, adsorption and incorporation into lipid membrane and formation of lipid/protein hybrid structures

Contact Info

Product

Resources

About