Dimerization and substrate recognition of human taurine transporter

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Physiology

Background:

• Taurine is a vital amino acid with numerous physiological roles, essential for cellular functions.
• Cellular taurine uptake is mainly regulated by the taurine transporter (TauT).
• TauT dysfunction is linked to serious health issues, including retinal, cardiac, and neurological disorders, as well as aging.

Purpose of the Study:

• To elucidate the structural mechanisms underlying taurine transport by TauT.
• To determine the structures of TauT in distinct functional states, including substrate-bound and apo forms.
• To investigate the structural basis of TauT dimerization and its implications for function.

Main Methods:

• Determination of TauT structures using X-ray crystallography in apo and substrate-bound states.
• Characterization of TauT in monomeric and dimeric forms, with a focus on the role of cholesterol.
• Functional assays to assess substrate recognition, specificity, and transport mechanisms.

Main Results:

• Structures of TauT were resolved in both inward-facing open and occluded states, bound to taurine or GABA.
• TauT exists as a dimer, stabilized by cholesterol molecules acting as 'molecular glue' between protomers.
• Detailed insights into substrate binding, specificity, and the transport cycle of TauT were obtained.

Conclusions:

• The determined structures provide a comprehensive framework for understanding TauT's mechanism of action.
• The findings illuminate the structural basis of substrate transport and specificity.
• This research offers a foundation for developing therapeutic strategies targeting TauT for taurine-deficiency disorders.