BioPHYSICAL chemistry

found in many different cell types but the mutations lead to termination
of growth only for motor neurons. The protein plays a role in RNA meta-
bolism as it has essential interactions with spliceosomes that participate
in pre-mRNA processing (Meister et al. 2002; Gubitz et al. 2004).
The determination of the SMN structure has not been possible, owing
to a number of difficulties with sample preparation. In structural analysis,
a common approach towards overcoming such difficulties is to work with a
smaller portion that is biochemically more tractable. This strategy proved
useful for the Tudor domain of SMN, which was
solved using NMR. The Tudor domain was expressed
in Escherichia coliand purified, and distance restraints
were derived primarily from nuclear Overhauser
enhancement spectroscopy. The resulting structure
was well defined with a high number of restraints
for each amino acid residue (Table 16.3).
Programs use the distance constraints with the
known geometric constraints, using energy minim-
ization to generate possible structures. Becausethe
final answer is not unique, a series of structures is
usually presented, each of which is possible given
all of the information (Figure 16.13). Differences
reflect both uncertainties in the assignments and dis-
order in the structure and provide a measure of the
coordinate precision in the structure determination
(Table 16.3).
The Tudor domain of SMN was found to fold
as a strongly bent antiparallel β sheet with the β
strands connected by short loops (Figure 16.14).
The structure has a number of features that could
not be identified easily from the sequence, such
as a negatively charged surface that is proposed to
interact with another class of proteins, termed Sm
proteins. One of the amino acid residues on the

CHAPTER 16 MAGNETIC RESONANCE 359

Table 16.3

Structural statistics for the Tudor domain. From Selenko et al. (2001).

Number of distance restraints 1402

Coordinate precision N, Cα, C 0.42 ±0.09

Ramachandran plot

Most favored 80.0 ±4.1

Additional allowed 19.8 ±4.1

Figure 16.13A superposition of 20

allowed structures of the Tudor domain.