gp210 is a major constituent of the nuclear pore complex (NPC) with possible 
structural and regulatory roles. It interacts with components of the NPC via its 
C-terminal domain (CTD), which follows a transmembrane domain and a massive ( 
approximately 200 kDa) N-terminal region that resides in the lumen of the 
perinuclear space. Here, we report the solution structure of the human gp210 CTD 
as determined by various spectroscopic techniques. In water, the CTD adopts an 
extended, largely unordered conformation, which contains a significant amount of 
left-handed polyproline type II (PII) helical structure. The conformation of the 
CTD is altered by high pH, charged detergents, and the hydrogen bond-promoting 
reagent trifluoroethanol (TFE), which decrease the PII fraction of the fragment. 
TFE also induces a conformational change in a region containing an SPXX motif 
whose serine becomes specifically phosphorylated during mitosis. We propose that 
PII elements in the CTD may play a role in its interaction with the NPC and may 
serve as recognition sites for regulatory proteins bearing WW or other, unknown 
PII-binding motifs.