Deep mutational scanning to probe specificity determinants in proteins

Bhowmick, Jayantika; Chandra, Soumyanetra; Varadarajan, Raghavan

doi:10.1016/b978-0-323-99533-7.00005-4

Cited by 6 publications

(5 citation statements)

References 244 publications

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“…Therefore, Arg is among the disorder-promoting amino acid. The charge combined with hydrophobicity and side chain flexibility are deciding factors for this propensity [22].…”

Section: Arginine In Protein Structure and Intrinsic Disordermentioning

confidence: 99%

Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins

Gupta,

Uversky

2024

International Journal of Biological Macromolecules

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“…Therefore, Arg is among the disorder-promoting amino acid. The charge combined with hydrophobicity and side chain flexibility are deciding factors for this propensity [22].…”

Section: Arginine In Protein Structure and Intrinsic Disordermentioning

confidence: 99%

Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins

Gupta,

Uversky

2024

International Journal of Biological Macromolecules

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“…When we talk about the low sequence complexity of IDPs/IDRs (especially those with extended disorder), we imply that their sequences are deficient in hydrophobic amino acids, such as Ile, Leu, Val, Phe, and Trp. IDPs/ IDRs are indeed found to be depleted in these as well as Cys and Asn (Bhowmick et al, 2023;Campen et al, 2008;Dunker et al, 2001;Radivojac et al, 2007;Williams et al, 2001). On the other hand, comprehensive computational analysis revealed that even well-folded ordered proteins do not always use the whole set of 20 amino acids, being characterized by the lower bounds for the alphabet size and Shannon's information entropy of 10 and $2.9, respectively (Romero et al, 1999).…”

Section: Some Amino Acids Enable Intrinsic Disorder In Proteinsmentioning

confidence: 99%

“…On the surfaces interacting with IDPs, Trp occurs most frequently and is followed by Arg (Jones et al, 2019; Jones & Thornton, 1997). The adequate hydrophobicity and flexibility enable Arg for this stellar role (Bhowmick et al, 2023). Recently, the π‐bonds of its guanidino group, already well known for its role in cation–π interactions, have also been reported to be responsible for fibril formation by stacking (Ferrari et al, 2020; Gallivan & Dougherty, 1999).…”

Section: Some Amino Acids Enable Intrinsic Disorder In Proteinsmentioning

confidence: 99%

Protein structure–function continuum model: Emerging nexuses between specificity, evolution, and structure

Gupta,

Uversky

2024

Protein Science

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The rationale for replacing the old binary of structure–function with the trinity of structure, disorder, and function has gained considerable ground in recent years. A continuum model based on the expanded form of the existing paradigm can now subsume importance of both conformational flexibility and intrinsic disorder in protein function. The disorder is actually critical for understanding the protein–protein interactions in many regulatory processes, formation of membrane‐less organelles, and our revised notions of specificity as amply illustrated by moonlighting proteins. While its importance in formation of amyloids and function of prions is often discussed, the roles of intrinsic disorder in infectious diseases and protein function under extreme conditions are also becoming clear. This review is an attempt to discuss how our current understanding of protein function, specificity, and evolution fit better with the continuum model. This integration of structure and disorder under a single model may bring greater clarity in our continuing quest for understanding proteins and molecular mechanisms of their functionality.

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“…Since deep mutational scanning represents a fast and convenient way of acquiring knowledge on the residue-specific contribution to protein interactions involving IDPs, it is likely that such approaches will be able to further shed light on ways by which molten globules play a biological role beyond being only folding intermediates [302].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins

Gupta

Uversky

2023

IJMS

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Transitions between the unfolded and native states of the ordered globular proteins are accompanied by the accumulation of several intermediates, such as pre-molten globules, wet molten globules, and dry molten globules. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

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Deep mutational scanning to probe specificity determinants in proteins

Cited by 6 publications

References 244 publications

Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins

Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins

Protein structure–function continuum model: Emerging nexuses between specificity, evolution, and structure

Pre-Molten, Wet, and Dry Molten Globules en Route to the Functional State of Proteins

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