Hidden Structural Codes in Protein Intrinsic Disorder
Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparallele...
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2017
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v56_n41_p5560_Borkosky http://hdl.handle.net/20.500.12110/paper_00062960_v56_n41_p5560_Borkosky |
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paper:paper_00062960_v56_n41_p5560_Borkosky2023-06-08T14:30:50Z Hidden Structural Codes in Protein Intrinsic Disorder Amino acids Biology Codes (symbols) Conformations Conformational ensemble Experimental methods Human papilloma virus Intrinsic disorder Intrinsically disordered proteins Protein intrinsic disorders Structural elements Structure-function correlation Proteins leucine oncoprotein viral protein intrinsically disordered protein leucine oncogene protein E7, Human papillomavirus type 16 peptide fragment protein E7 recombinant protein virus DNA alpha helix amino terminal sequence Article beta sheet controlled study correlational study mutation nonhuman nuclear magnetic resonance oligomerization Papillomaviridae priority journal protein analysis protein conformation protein domain protein folding protein function protein intrinsic disorder protein structure residue analysis virus genome amino acid sequence amino acid substitution chemistry comparative study conserved sequence gene deletion genetics Human papillomavirus type 16 metabolism molecular model nucleotide sequence pH point mutation protein stability sequence alignment site directed mutagenesis Amino Acid Sequence Amino Acid Substitution Base Sequence Conserved Sequence DNA, Viral Gene Deletion Human papillomavirus 16 Hydrogen-Ion Concentration Intrinsically Disordered Proteins Leucine Models, Molecular Mutagenesis, Site-Directed Papillomavirus E7 Proteins Peptide Fragments Point Mutation Protein Conformation Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Folding Protein Stability Recombinant Proteins Sequence Alignment Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble. © 2017 American Chemical Society. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v56_n41_p5560_Borkosky http://hdl.handle.net/20.500.12110/paper_00062960_v56_n41_p5560_Borkosky |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Amino acids Biology Codes (symbols) Conformations Conformational ensemble Experimental methods Human papilloma virus Intrinsic disorder Intrinsically disordered proteins Protein intrinsic disorders Structural elements Structure-function correlation Proteins leucine oncoprotein viral protein intrinsically disordered protein leucine oncogene protein E7, Human papillomavirus type 16 peptide fragment protein E7 recombinant protein virus DNA alpha helix amino terminal sequence Article beta sheet controlled study correlational study mutation nonhuman nuclear magnetic resonance oligomerization Papillomaviridae priority journal protein analysis protein conformation protein domain protein folding protein function protein intrinsic disorder protein structure residue analysis virus genome amino acid sequence amino acid substitution chemistry comparative study conserved sequence gene deletion genetics Human papillomavirus type 16 metabolism molecular model nucleotide sequence pH point mutation protein stability sequence alignment site directed mutagenesis Amino Acid Sequence Amino Acid Substitution Base Sequence Conserved Sequence DNA, Viral Gene Deletion Human papillomavirus 16 Hydrogen-Ion Concentration Intrinsically Disordered Proteins Leucine Models, Molecular Mutagenesis, Site-Directed Papillomavirus E7 Proteins Peptide Fragments Point Mutation Protein Conformation Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Folding Protein Stability Recombinant Proteins Sequence Alignment |
| spellingShingle |
Amino acids Biology Codes (symbols) Conformations Conformational ensemble Experimental methods Human papilloma virus Intrinsic disorder Intrinsically disordered proteins Protein intrinsic disorders Structural elements Structure-function correlation Proteins leucine oncoprotein viral protein intrinsically disordered protein leucine oncogene protein E7, Human papillomavirus type 16 peptide fragment protein E7 recombinant protein virus DNA alpha helix amino terminal sequence Article beta sheet controlled study correlational study mutation nonhuman nuclear magnetic resonance oligomerization Papillomaviridae priority journal protein analysis protein conformation protein domain protein folding protein function protein intrinsic disorder protein structure residue analysis virus genome amino acid sequence amino acid substitution chemistry comparative study conserved sequence gene deletion genetics Human papillomavirus type 16 metabolism molecular model nucleotide sequence pH point mutation protein stability sequence alignment site directed mutagenesis Amino Acid Sequence Amino Acid Substitution Base Sequence Conserved Sequence DNA, Viral Gene Deletion Human papillomavirus 16 Hydrogen-Ion Concentration Intrinsically Disordered Proteins Leucine Models, Molecular Mutagenesis, Site-Directed Papillomavirus E7 Proteins Peptide Fragments Point Mutation Protein Conformation Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Folding Protein Stability Recombinant Proteins Sequence Alignment Hidden Structural Codes in Protein Intrinsic Disorder |
| topic_facet |
Amino acids Biology Codes (symbols) Conformations Conformational ensemble Experimental methods Human papilloma virus Intrinsic disorder Intrinsically disordered proteins Protein intrinsic disorders Structural elements Structure-function correlation Proteins leucine oncoprotein viral protein intrinsically disordered protein leucine oncogene protein E7, Human papillomavirus type 16 peptide fragment protein E7 recombinant protein virus DNA alpha helix amino terminal sequence Article beta sheet controlled study correlational study mutation nonhuman nuclear magnetic resonance oligomerization Papillomaviridae priority journal protein analysis protein conformation protein domain protein folding protein function protein intrinsic disorder protein structure residue analysis virus genome amino acid sequence amino acid substitution chemistry comparative study conserved sequence gene deletion genetics Human papillomavirus type 16 metabolism molecular model nucleotide sequence pH point mutation protein stability sequence alignment site directed mutagenesis Amino Acid Sequence Amino Acid Substitution Base Sequence Conserved Sequence DNA, Viral Gene Deletion Human papillomavirus 16 Hydrogen-Ion Concentration Intrinsically Disordered Proteins Leucine Models, Molecular Mutagenesis, Site-Directed Papillomavirus E7 Proteins Peptide Fragments Point Mutation Protein Conformation Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Folding Protein Stability Recombinant Proteins Sequence Alignment |
| description |
Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble. © 2017 American Chemical Society. |
| title |
Hidden Structural Codes in Protein Intrinsic Disorder |
| title_short |
Hidden Structural Codes in Protein Intrinsic Disorder |
| title_full |
Hidden Structural Codes in Protein Intrinsic Disorder |
| title_fullStr |
Hidden Structural Codes in Protein Intrinsic Disorder |
| title_full_unstemmed |
Hidden Structural Codes in Protein Intrinsic Disorder |
| title_sort |
hidden structural codes in protein intrinsic disorder |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v56_n41_p5560_Borkosky http://hdl.handle.net/20.500.12110/paper_00062960_v56_n41_p5560_Borkosky |
| _version_ |
1768544252774580224 |