Evolving concepts of the protein universe
Summary: The protein universe is the collection of all proteins on earth from all organisms both extant and extinct. Classical studies on protein folding suggested that proteins exist as a unique three-dimensional conformation that is dictated by the genetic code and is critical for function. In thi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422500272X |
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| author | Prakash Kulkarni Lauren Porter Tsui-Fen Chou Shasha Chong Fabrizio Chiti Joseph W. Schafer Atish Mohanty Sravani Ramisetty Jose N. Onuchic Mick Tuite Vladimir N. Uversky Keith R. Weninger Eugene V. Koonin John Orban Ravi Salgia |
| author_facet | Prakash Kulkarni Lauren Porter Tsui-Fen Chou Shasha Chong Fabrizio Chiti Joseph W. Schafer Atish Mohanty Sravani Ramisetty Jose N. Onuchic Mick Tuite Vladimir N. Uversky Keith R. Weninger Eugene V. Koonin John Orban Ravi Salgia |
| author_sort | Prakash Kulkarni |
| collection | DOAJ |
| description | Summary: The protein universe is the collection of all proteins on earth from all organisms both extant and extinct. Classical studies on protein folding suggested that proteins exist as a unique three-dimensional conformation that is dictated by the genetic code and is critical for function. In this perspective, we discuss ideas and developments that emerged over the past three decades regarding the protein structure-function paradigm. It is now clear that ordered (active/functional) and disordered/denatured (and hence inactive/non-functional) represent a continuum of states rather than binary states. Some proteins can switch folds without sequence change. Others exist as conformational ensembles lacking defined structure yet play critical roles in many biological processes, including forming membrane-less organelles driven by liquid-liquid phase separation. Numerous diverse proteins harbor segments with the potential to form amyloid fibrils, many of which are functional, and some possess prion-like properties enabling conformation-based transfer of heritable information. Taken together, these developments reveal the remarkable complexity of the protein universe. |
| format | Article |
| id | doaj-art-d90ad7dc594047fab363bdd6c8352d60 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-d90ad7dc594047fab363bdd6c8352d602025-08-20T02:47:21ZengElsevieriScience2589-00422025-03-0128311201210.1016/j.isci.2025.112012Evolving concepts of the protein universePrakash Kulkarni0Lauren Porter1Tsui-Fen Chou2Shasha Chong3Fabrizio Chiti4Joseph W. Schafer5Atish Mohanty6Sravani Ramisetty7Jose N. Onuchic8Mick Tuite9Vladimir N. Uversky10Keith R. Weninger11Eugene V. Koonin12John Orban13Ravi Salgia14Department of Medical Oncology, City of Hope Medical Center, Duarte, CA, USA; Department of Systems Biology, City of Hope Medical Center, Duarte, CA, USA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Corresponding authorNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USADivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USADivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USADepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USADepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USADepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USACenter for Theoretical Biological Physics, Rice University, Houston, TX, USA; Department of Physics and Astronomy, Rice University, Houston, TX, USAKent Fungal Group, School of Biosciences, Division of Natural Sciences, University of Kent, CT2 7NJ Canterbury, UKDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Corresponding authorDepartment of Physics, North Carolina State University, Raleigh, NC, USANational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; Corresponding authorW. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA; Corresponding authorDepartment of Medical Oncology, City of Hope Medical Center, Duarte, CA, USA; Corresponding authorSummary: The protein universe is the collection of all proteins on earth from all organisms both extant and extinct. Classical studies on protein folding suggested that proteins exist as a unique three-dimensional conformation that is dictated by the genetic code and is critical for function. In this perspective, we discuss ideas and developments that emerged over the past three decades regarding the protein structure-function paradigm. It is now clear that ordered (active/functional) and disordered/denatured (and hence inactive/non-functional) represent a continuum of states rather than binary states. Some proteins can switch folds without sequence change. Others exist as conformational ensembles lacking defined structure yet play critical roles in many biological processes, including forming membrane-less organelles driven by liquid-liquid phase separation. Numerous diverse proteins harbor segments with the potential to form amyloid fibrils, many of which are functional, and some possess prion-like properties enabling conformation-based transfer of heritable information. Taken together, these developments reveal the remarkable complexity of the protein universe.http://www.sciencedirect.com/science/article/pii/S258900422500272XBiological sciencesBiochemistryProteinStructural biology |
| spellingShingle | Prakash Kulkarni Lauren Porter Tsui-Fen Chou Shasha Chong Fabrizio Chiti Joseph W. Schafer Atish Mohanty Sravani Ramisetty Jose N. Onuchic Mick Tuite Vladimir N. Uversky Keith R. Weninger Eugene V. Koonin John Orban Ravi Salgia Evolving concepts of the protein universe iScience Biological sciences Biochemistry Protein Structural biology |
| title | Evolving concepts of the protein universe |
| title_full | Evolving concepts of the protein universe |
| title_fullStr | Evolving concepts of the protein universe |
| title_full_unstemmed | Evolving concepts of the protein universe |
| title_short | Evolving concepts of the protein universe |
| title_sort | evolving concepts of the protein universe |
| topic | Biological sciences Biochemistry Protein Structural biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422500272X |
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