Ran in Nucleocytoplasmic Transport - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 109

switch II
loop

switch I
loop

C

C

Fig. 6.2 Conformational changes in Ran associated with different nucleotide-bound states.
Crystal structures of Ran in the GTP-bound ( gray , black ; PDB accession code 1RRP, Vetter
et al. 1999b ) and GDP-bound forms ( pink , red ; PDB accession code 1BYU, Stewart et al. 1998b ).
In common with other Ran-family GTPases, there are major conformational changes in the switch
I and switch II loops between the GTP-bound form ( black ) and the GDP-bound form ( red ), but in
Ran there is also a major conformational change at the C-terminus following residue 176. In the
GDP-bound form, the C-terminal region binds to a positive patch centered on residue 150, whereas
in the GTP-bound form, the position of the C-terminus differs depending on the protein to which
Ran is bound. The structure shown here is from the complex between RanGTP and a Ran-binding
domain of RanBP2 (Vetter et al. 1999b )

unstructured linker followed by a 16-residue -helical extension followed by an

acidic DEDDDL motif that is not observed in other Ras-family members
(Scheffzek et al. 1995 ). This C-terminal region is crucial in orchestrating the
interaction of Ran with karyopherin family transport factors and is essential to
defining the structure of GDP-bound Ran (Nilsson et al. 2002 ). Remarkably the
GDP-bound form of Ran in which this domain has been removed by truncation at
residue 176 has the properties and structure of the GTP-bound form (Nilsson
et al. 2002 ; Matsuura and Stewart 2004 ). In the GDP-bound state, the C-terminal
region is in contact with the Ras-like core of Ran (Scheffzek et al. 1995 ), whereas in
the GTP-bound state it extends away from this core (Vetter et al. 1999a , b ),
probably as a result of a steric clash between the switch I loop and the unstructured
linker region (Nilsson et al. 2002 ). Because of the way in which it mimics the
GTP-bound state, Ran truncated at residue 176 has been invaluable for obtaining
crystal structures of its complexes with karyopherin family transport factors (see,
for example, Matsuura and Stewart 2004 ; Lee et al. 2005 ; Cook et al. 2009 ;
Monecke et al. 2009 ; Okada et al. 2009 ; Koyama and Matsuura 2010 ).

α

Fig. 6.1 (continued) the cargo is released following GTP hydrolysis and the karyopherin recycled
to the nucleus. In both import and export pathways, the RanGDP generated in the cytoplasm is
recycled to the nucleus by NTF2 where RanGTP is regenerated by the RanGEF, RCC1