The impact of length variations in the L2 loop on the structure and thermal stability of non-specific porins: The case of OmpCs from the Yersinia pseudotuberculosis complex

Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):515-525. doi: 10.1016/j.bbamem.2017.10.014. Epub 2017 Oct 14.

Abstract

Porins are integral proteins of the outer membranes of gram-negative bacteria. In membranes, they exist as homotrimers and the L2 loops contribute to their stability. Comparison of OmpC porins of the Yersinia pseudotuberculosis complex with other enterobacterial porins demonstrated L2 loop length diversity, which is caused by varying numbers of dipeptide/tripeptide repeats. The OmpC porins are highly homologous to each other, and they can be subdivided into five isoforms based on their L2 loop structure. Optical spectroscopy and SDS-PAGE experiments revealed that particularities of the L2 loops affected the structure and thermal stability of the porins. Thermal denaturation studies showed that porins with shorter loops, compared to porins with longer loops, had more stable tertiary and less stable secondary and quaternary structures. According to our comparative modeling results, the L2 loops differ in their structure by adopting different spatial positions and forming different polar bonds with a neighbor monomer. The replacement of asparagine with arginine at the C-terminus of the L2 loop shifts the loop upwards and causes the loss of contacts with the arginine clusters within the pores. The increase in the length of these loops ensures that they shift down toward the pore and restore their contacts with arginines on the channel wall, as is the case in classical nonspecific porins. Despite the fact that the surface charge density varies considerably among the OmpC porins, the L2 loops form a typical negatively charged region in the center of the trimer.

Keywords: Computer modeling; OmpC isoforms; Optical spectroscopy; Porin; Thermal stability; Yersinia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Circular Dichroism
  • Models, Molecular
  • Phylogeny
  • Polymorphism, Genetic*
  • Porins / chemistry
  • Porins / genetics*
  • Porins / metabolism
  • Protein Conformation
  • Protein Multimerization
  • Protein Stability
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • Temperature
  • Yersinia pseudotuberculosis / classification
  • Yersinia pseudotuberculosis / genetics*
  • Yersinia pseudotuberculosis / metabolism

Substances

  • Bacterial Proteins
  • OmpC protein
  • Porins