Modeling Macromolecular Complexes: A Journey Across Scales - Modeling in Computational Biology and Biomedicine - page 24

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Fig. 1.8 The nuclear pore complex at different scales. ( a ) Level set surfaces representing all the
proteins of the NPC. The outer ring anchors the NPC in the nuclear membrane, while the inner
channel serves the nucleo-cytoplasmic transport. The diameter of the NPC is circa 100 nm. ( b )An
atomic resolution model of the so-called Y-complex, a sub-complex of nuclear pore complex.
(Adapted from [ 38 ])

(NPC), which is illustrated at two different scales on Fig. 1.8 . First, we explain
why the reconstruction of large assemblies such as the NPC yields ambiguous
results; second, we present a geometric modeling paradigm that accommodates
ambiguities on the shapes and positions of proteins within an assembly; finally, we
present selected tools allowing one to quantitatively bridge the gap between global-
ambiguous models, and local—atomic-resolution ones.

1.3.1 Challenges

1.3.1.1 From Atoms to Assemblies: Jumping Across

Three Orders of Magnitude

The largest protein complex known to date in eukaryotic cells is the nuclear
pore complex (NPC), which raises prototypical difficulties for modeling large
assemblies.
The NPC consists of about 456 protein instances of 30 protein types. Where
appropriate, we speak of protein types and protein instances (or types and instances
for short), instead of proteins. It is a cylindrical 100 nm-wide channel between the
nucleus and the cytoplasm, with a lumen of circa 40 nm. It is involved in the passive
diffusion of small molecules, and the active transport of large ones, with RNA
moving from the nucleus into the cytoplasm, and selected proteins synthesized in
the cytoplasm moving back into the nucleus. The NPC has eightfold axial symmetry,
and an approximate twofold rotational symmetry between the nucleoplasmic and
the cytosolic halves, yielding 16 so-called half-spokes . Its architecture has been
abstracted into four concentric cylinders [ 34 ], which are