Co-Translational Folding of Multi-Domain Proteins

Rajasekaran, Nandakumar; Kaiser, Christian

doi:10.3389/fmolb.2022.869027

Cited by 13 publications

(9 citation statements)

References 93 publications

(119 reference statements)

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“…Previous studies suggest that isolated domains of multidomain proteins may dimerize (or oligomerize) using the native-like interface, even without the enhancement of high local domain concentrations. 78 Based on the symmetrical nature of the domain interface in c 4 , one would expect both c 4 -A and c 4 -B to dimerize in their ferric state, but it is not the observation here. Therefore, we considered if perhaps other, non-native, interface sites are being used when ferric c 4 -A dimerizes.…”

Section: Structure Of Diheme Ps C 4 and Comparison Withmentioning

confidence: 77%

“…While ferric c 4 -B is a monomer at pH 5.0, ferric c 4 -A is a dimer. Previous studies suggest that isolated domains of multidomain proteins may dimerize (or oligomerize) using the native-like interface, even without the enhancement of high local domain concentrations . Based on the symmetrical nature of the domain interface in c 4 , one would expect both c 4 -A and c 4 -B to dimerize in their ferric state, but it is not the observation here.…”

Section: Discussionmentioning

confidence: 99%

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Influence of the Interdomain Interface on Structural and Redox Properties of Multiheme Proteins

et al. 2022

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Multiheme proteins are important in energy conversion and biogeochemical cycles of nitrogen and sulfur. A diheme cytochrome c 4 (c 4) was used as a model to elucidate roles of the interdomain interface on properties of iron centers in its hemes A and B. Isolated monoheme domains c 4-A and c 4-B, together with the full-length diheme c 4 and its Met-to-His ligand variants, were characterized by a variety of spectroscopic and stability measurements. In both isolated domains, the heme iron is Met/His-ligated at pH 5.0, as in the full-length c 4, but becomes His/His-ligated in c 4-B at higher pH. Intradomain contacts in c 4-A are minimally affected by the separation of c 4-A and c 4-B domains, and isolated c 4-A is folded. In contrast, the isolated c 4-B is partially unfolded, and the interface with c 4-A guides folding of this domain. The c 4-A and c 4-B domains have the propensity to interact even without the polypeptide linker. Thermodynamic cycles have revealed properties of monomeric folded isolated domains, suggesting that ferrous (FeII), but not ferric (FeIII) c 4-A and c 4-B, is stabilized by the interface. This study illustrates the effects of the interface on tuning structural and redox properties of multiheme proteins and enriches our understanding of redox-dependent complexation.

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Section: Structure Of Diheme Ps C 4 and Comparison Withmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Influence of the Interdomain Interface on Structural and Redox Properties of Multiheme Proteins

et al. 2022

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“…This internal cohesiveness is usually assessed through its effect on the chain dimensions such as the radius of gyration, end-to-end distance, hydrodynamic radius or the height extension of surface grafted chains [ 5 ]. The dependence of the IDP dimensions on their sequence is important in many other biological systems, such as inter-domain linkers in multi-domain macromolecules, small linear motifs and transcription factors [ 6 , 7 , 9 , 10 ].…”

Section: Resultsmentioning

confidence: 99%

“…In another important example of IDR function, IDRs serve as linkers between different folded domains of multi-domain proteins, in signaling and other processes [ 6 , 7 , 8 ]. In some cases, the properties of such linkers can be understood based on coarse grained polymer physics models, but the effects of sequence details are still incompletely understood [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…These results raise important fundamental questions about the methodologies of inference of the chain dimensions and internal structures of IDPs from the experimental data, which may depend on the specific assumptions in the polymer models used [ 42 , 43 ]. The dependence of the end-to-end distance on the biophysical properties of an IDR may also play an important role in the folding and misfolding of multi-domain proteins and in the efficiency of kinase phosphorylation efficiency [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Sequence Composition, Patterning and Hydrodynamics on the Conformation and Dynamics of Intrinsically Disordered Proteins

Vovk

Zilman

2023

IJMS

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Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) perform diverse functions in cellular organization, transport and signaling. Unlike the well-defined structures of the classical natively folded proteins, IDPs and IDRs dynamically span large conformational and structural ensembles. This dynamic disorder impedes the study of the relationship between the amino acid sequences of the IDPs and their spatial structures and dynamics, with different experimental techniques often offering seemingly contradictory results. Although experimental and theoretical evidence indicates that some IDP properties can be understood based on their average biophysical properties and amino acid composition, other aspects of IDP function are dictated by the specifics of the amino acid sequence. We investigate the effects of several key variables on the dimensions and the dynamics of IDPs using coarse-grained polymer models. We focus on the sequence “patchiness” informed by the sequence and biophysical properties of different classes of IDPs—and in particular FG nucleoporins of the nuclear pore complex (NPC). We show that the sequence composition and patterning are well reflected in the global conformational variables such as the radius of gyration and hydrodynamic radius, while the end-to-end distance and dynamics are highly sequence-specific. We find that in good solvent conditions highly heterogeneous sequences of IDPs can be well mapped onto averaged minimal polymer models for the purpose of prediction of the IDPs dimensions and dynamic relaxation times. The coarse-grained simulations are in a good agreement with the results of atomistic MD. We discuss the implications of these results for the interpretation of the recent experimental measurements, and for the further applications of mesoscopic models of FG nucleoporins and IDPs more broadly.

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How protein fold: Insights from nuclear magnetic resonance spectroscopy

Zhuravelva

2024

Encyclopedia of Condensed Matter Physics

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Co-Translational Folding of Multi-Domain Proteins

Cited by 13 publications

References 93 publications

Influence of the Interdomain Interface on Structural and Redox Properties of Multiheme Proteins

Influence of the Interdomain Interface on Structural and Redox Properties of Multiheme Proteins

Effects of Sequence Composition, Patterning and Hydrodynamics on the Conformation and Dynamics of Intrinsically Disordered Proteins

How protein fold: Insights from nuclear magnetic resonance spectroscopy

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