Crystal structure of human NIF3-like protein reveals dynamic hexameric assembly with a single divalent metal binding site.
TL;DR
The first crystal structures of human NIF3 are presented, revealing a hexameric toroidal assembly with a central cavity gated by PII-like insertion domains and a half-capped state with asymmetric disorder of the insertion domains.
Abstract
NIF3L1 (also NIF3) is a highly conserved protein belonging to the DUF34 protein family with unknown molecular function, present in bacteria, archaea, and eukaryotes. Here, we present the first crystal structures of human NIF3, revealing a hexameric toroidal assembly with a central cavity gated by PII-like insertion domains. Each subunit contains a mononuclear zinc-binding site, marking a clear departure from the dinuclear metal centers of bacterial homologs and potential functional divergence of the scaffold. We further capture a half-capped state with asymmetric disorder of the insertion domains and local rearrangements near the metal site, suggesting a gating mechanism that regulates access to the internal chamber. These findings uncover an unexpected level of structural plasticity in human NIF3 and provide a framework for future studies investigating whether the different lid conformations observed in our structures have functional relevance in vivo.