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Reformulation of an extant ATPase active site to mimic ancestral GTPase activity reveals a nucleotide base requirement for function.
Updegrove, Taylor B; Harke, Jailynn; Anantharaman, Vivek; Yang, Jin; Gopalan, Nikhil; Wu, Di; Piszczek, Grzegorz; Stevenson, David M; Amador-Noguez, Daniel; Wang, Jue D; Aravind, L; Ramamurthi, Kumaran S.
Affiliation
  • Updegrove TB; Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
  • Harke J; Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
  • Anantharaman V; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States.
  • Yang J; Department of Bacteriology, University of Wisconsin, Madison, United States.
  • Gopalan N; Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
  • Wu D; Biophysics Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
  • Piszczek G; Biophysics Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
  • Stevenson DM; Department of Bacteriology, University of Wisconsin, Madison, United States.
  • Amador-Noguez D; Department of Bacteriology, University of Wisconsin, Madison, United States.
  • Wang JD; Department of Bacteriology, University of Wisconsin, Madison, United States.
  • Aravind L; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States.
  • Ramamurthi KS; Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Elife ; 102021 03 11.
Article in En | MEDLINE | ID: mdl-33704064
Living organisms need energy to stay alive; in cells, this energy is supplied in the form of a small molecule called adenosine triphosphate, or ATP, a nucleotide that stores energy in the bonds between its three phosphate groups. ATP is present in all living cells and is often referred to as the energy currency of the cell, because it can be easily stored and transported to where it is needed. However, it is unknown why cells rely so heavily on ATP when a highly similar nucleotide called guanosine triphosphate, or GTP, could also act as an energy currency. There are several examples of proteins that originally used GTP and have since evolved to use ATP, but it is not clear why this switch occurred. One suggestion is that ATP is the more readily available nucleotide in the cell. To test this hypothesis, Updegrove, Harke et al. studied a protein that helps bacteria transition into spores, which are hardier and can survive in extreme environments until conditions become favorable for bacteria to grow again. In modern bacteria, this protein uses ATP to provide energy, but it evolved from an ancestral protein that used GTP instead. First, Updegrove, Harke et al. engineered the protein so that it became more similar to the ancestral protein and used GTP instead of ATP. When this was done, the protein gained the ability to break down GTP and release energy from it, but it no longer performed its enzymatic function. This suggests that both the energy released and the source of that energy are important for a protein's activity. Further analysis showed that the modern version of the protein has evolved to briefly hold on to ATP after releasing its energy, which did not happen with GTP in the modified protein. Updegrove, Harke et al. also discovered that the levels of GTP in a bacterial cell fall as it transforms into a spore, while ATP levels remain relatively high. This suggests that ATP may indeed have become the source of energy of choice because it was more available. These findings provide insights into how ATP became the energy currency in cells, and suggest that how ATP is bound by proteins can impact a protein's activity. Additionally, these experiments could help inform the development of drugs targeting proteins that bind nucleotides: it may be essential to consider the entirety of the binding event, and not just the release of energy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bacillus subtilis / Bacterial Proteins / Adenosine Triphosphatases / GTP Phosphohydrolases Language: En Journal: Elife Year: 2021 Document type: Article Affiliation country: Estados Unidos Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bacillus subtilis / Bacterial Proteins / Adenosine Triphosphatases / GTP Phosphohydrolases Language: En Journal: Elife Year: 2021 Document type: Article Affiliation country: Estados Unidos Country of publication: Reino Unido