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The HEAT 11/12 B helices can accommodate binding of both the C-terminal helix tip and the HEAT 9 loop. Alignment of S. cerevisiae Xpo1p (11) and human CRM1 (9) indicates that the two proposed interactions at the HEAT 11/12 B helices (in cyan) cleft could occur simultaneously. The HEAT 9 loop is shown in the conformation that promotes closure of the NES cleft at the HEAT 11/12 A helices.
