The novel class of seven transmembrane segment inverted repeat carriers

Area of Science:

• Membrane biology
• Structural biology
• Biochemistry

Background:

• Solute carriers (SLCs) from the SLC4, SLC23, and SLC26 families are crucial for cellular functions including pH regulation, vitamin C transport, and ion homeostasis.
• Despite functional similarities, these SLC families lack obvious sequence homology, suggesting a convergent evolution or a shared ancient origin.
• A unique structural architecture unites these families, characterized by two structurally related halves, each comprising seven transmembrane segments.

Purpose of the Study:

• To highlight the general design principles of the unique solute carrier fold shared by SLC4, SLC23, and SLC26 families.
• To reveal the structural diversity and functional variations among different families within this structural class.
• To detail the transport mechanism of this fold, informed by recent structural data.

Main Methods:

• Review of existing literature and analysis of recently solved structures of different SLC family members.
• Comparative analysis of domain architecture, structural framework, and transmembrane segment organization.
• Inference of transport mechanisms based on structural insights and functional data.

Main Results:

• The solute carrier fold is characterized by two inverted repeats, each consisting of seven transmembrane segments, forming an intricately intertwined structure.
• These two halves span the membrane with opposite orientations, contributing to a novel and conserved structural framework.
• Significant diversity exists in domain architecture, specific structural details, and transport modes across the SLC4, SLC23, and SLC26 families.

Conclusions:

• The conserved, unique architecture of SLC4, SLC23, and SLC26 families provides a common structural basis for their diverse transport functions.
• Understanding this fold's design principles and transport mechanisms offers insights into solute transport across biological membranes.
• Future research can leverage structural information to elucidate the precise mechanisms of pH regulation, vitamin C transport, and ion homeostasis mediated by these SLCs.