  Guanylate binding proteins (GBPs) are soluble dynamin-like proteins with
structured domains that undergo a conformational transition for GTP-controlled
oligomerization to exert their function as part of the innate immune system of
mammalian cells - attacking intra-cellular parasites by disrupting their
membranes. The structural basis and mechanism of this process is unknown.
Therefore, we apply neutron spin echo, X-ray scattering, fluorescence, and EPR
spectroscopy as techniques for integrative dynamic structural biology to human
GBP1 (hGBP1). We mapped hGBP1's essential dynamics from nanoseconds to
milliseconds by motional spectra of sub-domains. We find a GTP-independent
flexibility of the C-terminal effector domain in the $\mu$s-regime and
structurally characterize conformers being essential that hGBP1 can open like a
pocketknife for oligomerization. This unveils the intrinsic flexibility, a
GTP-triggered association of the GTPase-domains and assembly-dependent
GTP-hydrolysis as functional design principles of hGBP1 that control its
reversible oligomerization in polar assemblies and the subsequent formation of
condensates.
