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Fig. 7 Progress in integral membrane protein structure determination by solution NMR
(structures with more than one membrane-spanning segment only). The cumulative number of
integral membrane protein structures determined by solution NMR is shown for each year, starting
with the year the first high-resolution structure of a TM-helix dimer was revealed in 1997 [
140
]. As
had been shown for X-ray crystal structures of membrane proteins [
399
], this accumulation can be
fit to the equation
N
exp(
aY
), where
N
is the cumulative total of structures for each year
following publication of the first structure (
Y
). The scaling parameter
a
¼
0.236 for the best-fit
curve (shown as the
solid line
) is almost the same as that previously determined for membrane
protein X-ray structures (
a
¼
0.242), showing similar rates of progress for the two structure
determination techniques. Year 0 for X-ray crystal structures was recognized as 1985 [
399
],
more than 10 years earlier than that for NMR (1997). A useful reference used in the compilation
this data was provided by the on-line catalogue of membrane protein NMR structures (
http://www.
¼
structures of membrane proteins (Fig.
7
)[
387
], with the main disadvantage being its
late start relative to X-ray crystallography. Assuming that solution NMR of mem-
brane proteins continues at this pace, we can expect to see the 100 structure mark
surpassed in approximately 6 years. The ability of long-range restraints to be
acquired without the need for side chain assignment will be particularly important
in meeting these projections, as will the implementation of new sensitivity-enhanc-
ing technologies by an increasing number of labs. This analysis shows that, while
solution NMR studies of larger membrane proteins may not yet be routine, reaping
the rewards of these endeavors will become increasingly feasible for a larger range
of membrane proteins than ever before.
Acknowledgments This work was supported by the Natural Sciences and Engineering Research
Council (NSERC).
References
1. Kim H, Mel
´
n K, Osterberg M, von Heijne G (2006) A global topology map of the
Saccharomyces cerevisiae
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2. Almen MS, Nordstrom KJV, Fredriksson R, Schioth HB (2009) Mapping the human mem-
brane proteome: a majority of the human membrane proteins can be classified according to
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