Isolation and crystallization of copper resistance protein B (CopB) from Acinetobacter baumannii

Protein Expr Purif. 2025 Mar:227:106635. doi: 10.1016/j.pep.2024.106635. Epub 2024 Nov 26.

Abstract

Acinetobacter baumannii (A. baumannii) is an opportunistic, Gram-negative human pathogen, which is predominantly found in hospital patients. Its antimicrobial resistance is escalating, leading to less efficient treatments, and an increasing interest in identifying new therapeutic drugs. Metals as antimicrobials are vital in healthcare and agriculture, and copper-containing surfaces are known to reduce microbial counts, also in clinical settings. Indeed, copper (Cu) is an essential element required for survival in all organisms from bacteria to humans, but nevertheless elevated levels are highly toxic for cells. Through different regulatory mechanisms, cells maintain Cu homeostasis, and ion channels and transporters are critical in this process. Precise understanding of such ion transport requires insight into the protein structures of the involved proteins, which will also provide information important for applied sciences. Considering the medical significance of A. baumannii and the possibility to exploit Cu to handle such infections, channels and transporters represent appealing targets. Here we approached the putative outer membrane CopB (Copper resistance protein B) from A. baumannii that is postulated to conduct Cu, with characterization of its structure and function as well as to enable rational drug-design. To this end, we demonstrate in this work procedures to produce purified sample and to recover diffracting protein crystals of CopB. The protein was overproduced in E. coli and membrane extracted in a range of detergents. The solubilized protein was subjected to crystallization, which yielded hits that scatter X-rays to low resolution. Our findings have the potential to pave the way for subsequent drug discovery.

Keywords: Acinetobacter baumannii; Copper; Copper resistance protein B (CopB); Protein crystallization; Protein production; Protein purification.

Publication types

  • Review

MeSH terms

  • Acinetobacter baumannii* / chemistry
  • Acinetobacter baumannii* / drug effects
  • Acinetobacter baumannii* / genetics
  • Acinetobacter baumannii* / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / isolation & purification
  • Cation Transport Proteins / metabolism
  • Cloning, Molecular
  • Copper* / chemistry
  • Copper* / metabolism
  • Crystallization*
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Copper
  • Bacterial Proteins
  • Recombinant Proteins
  • Cation Transport Proteins