Does protein unfolding play a functional role in vivo?

How mechanical unfolding of proteins has a functional role in vivo is still poorly understood. In this review, we distill the main biophysical characteristics of multidomain proteins functioning under force as binary molecular computational units and examine them as part of several biological proces...

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Published inThe FEBS journal Vol. 288; no. 6; pp. 1742 - 1758
Main Authors Sharma, Sabita, Subramani, Smrithika, Popa, Ionel
Format Journal Article
LanguageEnglish
Published England Blackwell Publishing Ltd 01.03.2021
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Abstract How mechanical unfolding of proteins has a functional role in vivo is still poorly understood. In this review, we distill the main biophysical characteristics of multidomain proteins functioning under force as binary molecular computational units and examine them as part of several biological processes. Understanding the relation between molecular unfolding of proteins under force and their overall macroscopic impact can provide insight into novel mechanical signaling pathways and gain‐of‐function mechanisms. Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain‐of‐function from the perspective of a fine‐tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding‐induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano‐active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
AbstractList Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain‐of‐function from the perspective of a fine‐tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding‐induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano‐active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain-of-function from the perspective of a fine-tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding-induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano-active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo . In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain‐of‐function from the perspective of a fine‐tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding‐induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano‐active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain-of-function from the perspective of a fine-tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding-induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano-active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain-of-function from the perspective of a fine-tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding-induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano-active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
How mechanical unfolding of proteins has a functional role in vivo is still poorly understood. In this review, we distill the main biophysical characteristics of multidomain proteins functioning under force as binary molecular computational units and examine them as part of several biological processes. Understanding the relation between molecular unfolding of proteins under force and their overall macroscopic impact can provide insight into novel mechanical signaling pathways and gain‐of‐function mechanisms. Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain‐of‐function from the perspective of a fine‐tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding‐induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano‐active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
Author Subramani, Smrithika
Popa, Ionel
Sharma, Sabita
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Issue 6
Keywords cellular mechanotransduction
energy landscape
force spectroscopy
protein unfolding
bacterial adhesion
muscular contraction
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– ident: e_1_2_9_115_1
  doi: 10.1021/nn5044383
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Snippet How mechanical unfolding of proteins has a functional role in vivo is still poorly understood. In this review, we distill the main biophysical characteristics...
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo . In this review,...
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we...
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we...
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StartPage 1742
SubjectTerms Antibiotics
bacterial adhesion
batteries
cellular mechanotransduction
Contraction
Dystrophy
energy landscape
force spectroscopy
gain-of-function mutation
Mechanotransduction
Muscle contraction
muscular contraction
Muscular dystrophy
Protein folding
protein unfolding
Proteins
Structure-function relationships
Title Does protein unfolding play a functional role in vivo?
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Ffebs.15508
https://www.ncbi.nlm.nih.gov/pubmed/32761965
https://www.proquest.com/docview/2501870851
https://www.proquest.com/docview/2431805604
https://www.proquest.com/docview/2524333622
Volume 288
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