Nuclear localization of clathrin involves a labile helix outside the trimerization domain

Clathrin is a trimeric protein involved in receptor-mediated-endocytosis, but can function as a non-trimer outside of endocytosis. We have discovered that the subcellular distribution of a clathrin cysteine mutant we previously studied is altered and a proportion is also localized to nuclear spaces. MALS shows C1573A hub is a mixture of trimer-like and detrimerized molecules. The X-ray structure of the trimerization domain reveals that without light chains, a helix harboring cysteine-1573 is reoriented. We propose clathrin has a detrimerization switch, which suggests clathrin topology can be altered naturally for new functions.

► C1573A clathrin hub is localized to nuclear spaces.
► Cysteine-1573 in Helix 7j is essential for normal clathrin topology.
► Trimerization domain crystal structure is distorted without clathrin light chain.
► X-ray model suggests a detrimerization switch may mediate clathrin structure/function.