7CKF

The N-terminus of interferon-inducible antiviral protein-dimer

Summary for 7CKF

• Entry DOI: 10.2210/pdb7ckf/pdb
• Descriptor: Guanylate-binding protein 5, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: antiviral, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 71956.02

Authors

Cui, W.,Yang, H.T. (deposition date: 2020-07-16, release date: 2021-05-05, Last modification date: 2023-11-29)

Primary citation

Cui, W.,Braun, E.,Wang, W.,Tang, J.,Zheng, Y.,Slater, B.,Li, N.,Chen, C.,Liu, Q.,Wang, B.,Li, X.,Duan, Y.,Xiao, Y.,Ti, R.,Hotter, D.,Ji, X.,Zhang, L.,Cui, J.,Xiong, Y.,Sauter, D.,Wang, Z.,Kirchhoff, F.,Yang, H.
Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP5), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP5 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.

PubMed: 33876762
DOI: 10.1073/pnas.2022269118

Experimental method

X-RAY DIFFRACTION (2.284 Å)