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Functional and structural characterization of PII‐like protein CutA does not support involvement in heavy metal tolerance and hints at a small‐molecule carrying/signaling role

DOI: 10.1111/febs.15464 DOI Help

Authors: Khaled A. Selim (Tübingen University; Max Planck Institute for Developmental Biology) , Lorena Tremino (Instituto de Biomedicina de Valencia (IBV‐CSIC), CIBER de Enfermedades Raras (CIBERER‐ISCIII)) , Clara Marco-marin (Instituto de Biomedicina de Valencia (IBV‐CSIC), CIBER de Enfermedades Raras (CIBERER‐ISCIII)) , Vikram Alva (Max Planck Institute for Developmental Biology) , Javier Espinosa (Universidad de Alicante) , Asunción Contreras (Universidad de Alicante) , Marcus D. Hartmann (Max Planck Institute for Developmental Biology) , Karl Forchhammer (Tübingen University) , Vicente Rubio (Instituto de Biomedicina de Valencia (IBV‐CSIC), CIBER de Enfermedades Raras (CIBERER‐ISCIII))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Febs Journal , VOL 276

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 20229

Open Access Open Access

Abstract: The PII‐like protein CutA is annotated as being involved in Cu2+ tolerance, based on analysis of Escherichia coli mutants. However, the precise cellular function of CutA remains unclear. Our bioinformatic analysis reveals that CutA proteins are universally distributed across all domains of life. Based on sequence‐based clustering, we chose representative cyanobacterial CutA proteins for physiological, biochemical, and structural characterization and examined their involvement in heavy metal tolerance, by generating CutA mutants in filamentous Nostoc sp. and in unicellular Synechococcus elongatus . However, we were unable to find any involvement of cyanobacterial CutA in metal tolerance under various conditions. This prompted us to re‐examine experimentally the role of CutA in protecting E. coli from Cu2+. Since we found no effect on copper tolerance, we conclude that CutA plays a different role that is not involved in metal protection. We resolved high‐resolution CutA structures from Nostoc and S. elongatus . Similarly to their counterpart from E. coli and to canonical PII proteins, cyanobacterial CutA proteins are trimeric in solution and in crystal structure; however, no binding affinity for small signaling molecules or for Cu2+ could be detected. The clefts between the CutA subunits, corresponding to the binding pockets of PII proteins, are formed by conserved aromatic and charged residues, suggesting a conserved binding/signaling function for CutA. In fact, we find binding of organic Bis‐Tris/MES molecules in CutA crystal structures, revealing a strong tendency of these pockets to accommodate cargo. This highlights the need to search for the potential physiological ligands and for their signaling functions upon binding to CutA.

Journal Keywords: cyanobacteria; heavy metal tolerance; Nostoc sp. PCC 7120; PII superfamily; PII‐like protein CutA; signal transduction; Synechococcus elongatus PCC 7942

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography

Other Facilities: Swiss Light Source; ALBA


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