Quantitative comparison of ABC membrane protein type I exporter structures in a standardized way

Georgina Csizmadia; Bianka Farkas; Zoltán Spagina; Hedvig Tordai; Tamás Hegedűs

doi:10.1016/j.csbj.2018.10.008

Quantitative comparison of ABC membrane protein type I exporter structures in a standardized way

Comput Struct Biotechnol J. 2018 Oct 18:16:396-403. doi: 10.1016/j.csbj.2018.10.008. eCollection 2018.

Authors

Georgina Csizmadia^{1

2}, Bianka Farkas^{2

3}, Zoltán Spagina^{2

3}, Hedvig Tordai², Tamás Hegedűs^{1

2}

Affiliations

¹ MTA-SE Molecular Biophysics Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
² Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
³ Faculty of Information Technology, Pázmány Péter Catholic University, Budapest, Hungary.

Abstract

An increasing number of ABC membrane protein structures are determined by cryo-electron microscopy and X-ray crystallography, consequently identifying differences between their conformations has become an arising issue. Therefore, we propose to define standardized measures for ABC Type I exporter structure characterization. We set conformational vectors, conftors, which describe the relative orientation of domains and can highlight structural differences. In addition, continuum electrostatics calculations were performed to characterize the energetics of membrane insertion illuminating functionally crucial regions. In summary, the proposed metrics contribute to deeper understanding of ABC membrane proteins' structural features, structure validation, and analysis of movements observed in a molecular dynamics trajectory. Moreover, the concept of standardized metrics can be applied not only to ABC membrane protein structures (http://conftors.hegelab.org).

Keywords: ABC proteins; ABC, ATP binding cassette; CFTR, cystic fibrosis transmembrane conductance regulator; CG, coarse grained; CH, coupling helix; COG, center of geometry; ICD, intracellular domain; Membrane proteins; NBD, nucleotide binding domain; Quantitative structural properties; Structure comparison; Structure validation; TH, transmembrane helix; TM, transmembrane; TMD, transmembrane domain.