When two turn into one: evolution of membrane transporters from half modules

Area of Science:

• Biochemistry
• Structural Biology
• Evolutionary Biology

Background:

• Increasing atomic structures reveal conserved 'inverted repeat topology' in sequence-unrelated transporter families.
• Most membrane transporters feature repeating structural domains, suggesting evolution via duplication and fusion.
• The existence of independent 'half-transporter' units as evolutionary precursors is an open question.

Purpose of the Study:

• To explore the hypothesis that membrane transporters evolved from simpler repeating units.
• To identify potential 'half-transporter' candidates within existing protein families.
• To investigate the evolutionary link between putative half-transporters and major transporter families.

Main Methods:

• Review of existing structural and sequence data for membrane transporters.
• Comparative analysis of protein families with conserved structural motifs.
• Hypothesis-driven discussion of evolutionary pathways for transporter families.

Main Results:

• The 'inverted repeat topology' is a common feature across diverse transporter families.
• The DedA and SWEET protein families are proposed as potential half-transporter candidates.
• These families may represent ancestral forms for the abundant MFS and LeuT-fold transporter families.

Conclusions:

• Membrane transporter evolution likely involved the duplication and fusion of smaller structural units.
• DedA and SWEET families provide compelling evidence for the existence of functional half-transporters.
• Understanding these ancestral units offers insights into the evolution of complex transport systems.