Inverted topologies in membrane proteins: a mini-review.

Area of Science:

• Structural biology
• Biochemistry
• Evolutionary biology

Background:

• Helical membrane proteins like transporters and channels frequently exhibit structural symmetry.
• Homo-oligomers display perfect symmetry, while single-chain proteins often show internal pseudo-symmetry.
• Pseudo-symmetry in single-chain proteins can mirror folds of homo-oligomers, suggesting evolutionary gene duplication and fusion.

Purpose of the Study:

• To review helical transporter proteins exhibiting an inverted two-fold pseudo-symmetry.
• To explore the evolutionary implications of pseudo-symmetry in membrane protein development.
• To discuss how symmetry facilitates recognition of symmetric substrates like ions.

Main Methods:

• Review of existing literature on helical membrane proteins.
• Analysis of structural data for proteins with inverted two-fold pseudo-symmetry.
• Hypothetical modeling of evolutionary pathways.

Main Results:

• Inverted two-fold pseudo-symmetry is observed in helical transporter proteins, with the symmetry axis in the membrane plane.
• This symmetry suggests an ancestral monomer that could insert bidirectionally into the membrane.
• Conformations (open-to-inside and open-to-outside) may be structurally identical and iso-energetic.

Conclusions:

• Pseudo-symmetry in membrane proteins, particularly transporters, offers an evolutionary route to novel functionalities.
• The inverted two-fold symmetry provides a mechanism for creating transporter proteins that alternate between functional states.
• Symmetry is a key principle in the evolution and function of membrane transport proteins.