{"id":9484,"date":"2025-05-14T15:16:53","date_gmt":"2025-05-14T06:16:53","guid":{"rendered":"https:\/\/www.elsi.jp\/?post_type=news_events&p=9484"},"modified":"2025-05-14T15:41:22","modified_gmt":"2025-05-14T06:41:22","slug":"protein_problem","status":"publish","type":"news_events","link":"https:\/\/www.elsi.jp\/en\/news_events\/highlights\/2025\/protein_problem\/","title":{"rendered":"Protein problem: Researchers challenge fundamental assumption in evolutionary biochemistry"},"content":{"rendered":"

[This is a Joint Press Release with Georgia Institute of Technology]<\/strong>
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\nHow did life originate? Ancient proteins may hold important clues. Every organism on Earth is made up of proteins. Although all organisms \u2014 even single-celled ones \u2014 have complex protein structures now, this wasn\u2019t always the case.<\/strong>
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Image 1. Schematic representation of cofactor-bound Walker A P-loops. This figure is adapted from Demkiv et al., Mol. Biol. Evol. 2025, 42, msaf055, originally published under a CC-BY license. Credit: Molecular Biology and Evolution<\/em><\/div>\n

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For years, evolutionary biochemists assumed that the most ancient proteins emerged from a simple signature, called a motif. New research from, though, suggests that this motif, without the surrounding protein, isn\u2019t as consequential as it seemed. The international team of researchers was led by Lynn Kamerlin, a professor in the Georgia Tech School of Chemistry and Biochemistry and Georgia Research Alliance Vasser Woolley Chair in Molecular Design, and Liam Longo, a Specially Appointed Associate Professor at Earth-Life Science Institute (ELSI) at Institute of Science Tokyo, in Japan.<\/p>\n

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\u201cIt\u2019s probably an eroded molecular fossil, with its true nature having been overwritten over billions of years of evolution,\u201d said Kamerlin. \u201cThis work completely reshapes how we think about proteins. It\u2019s like trying to play protein Jeopardy! \u2014 now we need to rethink what the original question was.\u201d<\/p>\n

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Prehistoric Proteins<\/strong><\/p>\n

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It’s not hard to understand why this hypothesis was wrong for so long. The motif is associated with the element phosphorus, one of the key elements of life. Many of the earliest proteins bound to phosphorus-containing compounds. While these early proteins have different structures, they frequently share the same motif.<\/p>\n

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\u201cFor years, researchers took this to mean that today\u2019s complex proteins came from the motif itself \u2014 that this tiny protein gave rise to entire families,\u201d Longo said.<\/p>\n

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To discover the protein\u2019s origins, the researchers pored over available data on protein crystal structures. Then they identified and characterised relevant proteins computationally. Although they recognised some of the protein\u2019s similar structure in their modelling, the motif was not identical. They found that many different types of phosphate-binding proteins were possible. The idea that this motif was somehow special on its own was false.<\/p>\n

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\u201cWe don\u2019t hypothesise that eyes gave rise to heads, even though nearly all heads have eyes; that\u2019s because seeing involves interlocking systems,\u201d Kamerlin said. \u201cOur early peptide presents a similar instance. Only embedding within the larger system allows it to shine.\u201d<\/p>\n

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Protein Possibilities<\/strong><\/p>\n

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The researchers tested this work in water and methanol environments. Methanol mimics environments on Earth that may have less water around. The researchers found comparable protein motifs in this methanol environment, proving that the famous motif was not unique, but rather one of many possible motifs with similar properties. What was assumed to be a building block of early life is probably just a fossil fragment \u2014 and not the complete picture.<\/p>\n

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Kamerlin and Longo\u2019s work helps their field determine not just how life started but also bolsters biotechnology advancements. A better understanding of how natural proteins evolved will help other researchers create artificial proteins, for everything from drug delivery to new vaccines.<\/p>\n

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The work is far from finished. Now that the researchers know this protein motif is one of many possible options, the question becomes: When did this motif become dominant, and what else could life have looked like? These questions will help the scientific world make discoveries that could benefit everyone.<\/p>\n

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Funding from the Knut and Alice Wallenberg Foundation; the Okinawa Institute of Science and Technology Graduate University (OIST) with subsidy funding from the Cabinet Office, Government of Japan; and the National Academic Infrastructure for Supercomputing in Sweden.<\/p>\n

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Reference <\/strong><\/p>\n

Andrey O. Demkiv1<\/sup>, Saacnicteh Toledo-Pati\u00f1o2,3<\/sup>, Encarnaci\u00f3n Medina-Carmona4<\/sup>, Andrej Berg1<\/sup>, Gaspar P. Pinto1<\/sup>, Antonietta Parracino1<\/sup>, Jose M. Sanchez-Ruiz4<\/sup>, Alvan C. Hengge5<\/sup>, Paola Laurino2,6<\/sup>, Liam M. Longo7,8,*<\/sup>, Shina Caroline Lynn Kamerlin9,10,*<\/sup>, Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases, Molecular Biology and Evolution, <\/em>DOI: 10.1093\/molbev\/msaf055<\/a><\/p>\n

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  1. Department of Chemistry\u2014BMC, Uppsala University, Uppsala S-751 23, Sweden<\/li>\n
  2. Protein Engineering and Evolution Unit, Okinawa Institute of Science and Technology, Graduate University (OIST), Okinawa 904-0495, Japan<\/li>\n
  3. Molecular Bioengineering Group, Okinawa Institute of Science and Technology, Graduate University (OIST), Okinawa 904-0495, Japan<\/li>\n
  4. Departamento de Qu\u00edmica F\u00edsica, Facultad de Ciencias, Unidad de Excelencia de Qu\u00edmica aplicada a Biomedicina y Medioambiente (UEQ), Universidad de Granada, Granada 18071, Spain<\/li>\n
  5. Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA<\/li>\n
  6. Institute for Protein Research, Osaka University, Suita, Japan<\/li>\n
  7. Blue Marble Space Institute of Science, Seattle, WA 98104, USA<\/li>\n
  8. Earth-Life Science Institute, Institute of Science Tokyo, Tokyo 152-8550, Japan<\/li>\n
  9. School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA<\/li>\n
  10. Department of Chemistry, Lund University, Box 124, Lund 22100, Sweden<\/li>\n<\/ol>\n

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    *Corresponding authors email: llongo@elsi.jp, skamerlin3@gatech.edu.<\/p>\n

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    Contacts:<\/strong><\/p>\n

    Thilina Heenatigala
    \nDirector of Communications
    \nEarth-Life Science Institute (ELSI),
    \nInstitute of Science Tokyo
    \nE-mail: thilinah@elsi.jp
    \nTel: +81-3-5734-3163 \/ Fax: +81-3-5734-3416<\/p>\n

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    Liam M. Longo
    \nSpecially Appointed Associate Professor
    \nEarth-Life Science Institute (ELSI),
    \nInstitute of Science Tokyo
    \nEmail: llongo@elsi.jp<\/p>\n

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