Abstract
Guanylate binding proteins (GBPs) belong to the dynamin-related superfamily and exhibit various functions in the fight against infections. The functions of the human guanylate binding protein 1 (hGBP1) are tightly coupled to GTP hydrolysis and dimerization. Despite known crystal structures of the hGBP1 monomer and GTPase domain dimer, little is known about the dynamics of hGBP1. To gain a mechanistic understanding of hGBP1, we performed sub-millisecond multi-resolution molecular dynamics simulations of both the hGBP1 monomer and dimer. We found that hGBP1 is a highly flexible protein that undergoes a hinge motion similar to the movements observed for other dynamin-like proteins. Another large-scale motion was observed for the C-terminal helix α13, providing a molecular view for the α13–α13 distances previously reported for the hGBP1 dimer. Most of the loops of the GTPase domain were found to be flexible, revealing why GTP binding is needed for hGBP1 dimerization to occur.
Highlights
Guanosine triphosphate (GTP) binding proteins play essential roles in many cellular processes responsible for the maintenance and regulation of biological functions
In concert with the conversion of GTP the dimerization of human guanylate binding protein 1 (hGBP1) occurs, which can further interact with the lipid membrane of the pathogen and disrupt it
An alternative approach is given by molecular simulations, allowing us to elucidate the protein dynamics closely connected to these steps
Summary
Guanosine triphosphate (GTP) binding proteins play essential roles in many cellular processes responsible for the maintenance and regulation of biological functions. Among these proteins are the guanylate binding proteins (GBPs), which belong to the dynamin-related protein family, even though the GTPase domain is the only conserved sequence. They have various functions in the resistance against intracellular pathogens via GTP binding and hydrolysis [1,2,3,4,5]. The human guanylate binding protein 1 (hGBP1) was found to be involved in the defense against viruses, in particular against the vesicular stomatitis virus and the encephalomyocarditis virus, and bacteria [7, 8]. hGBP1 was identified as a marker of various cancer types, such as mammary cancer [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
