Cryo-EM structure of human ATR-ATRIP complex

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• The ATR-ATRIP complex is essential for cellular response to DNA damage and replication stress.
• Understanding the complex's structure is key to elucidating DNA repair mechanisms.

Purpose of the Study:

• To determine the high-resolution cryo-electron microscopy (EM) structure of the human ATR-ATRIP complex.
• To provide a structural basis for ATR-ATRIP complex assembly and function.

Main Methods:

• Cryo-electron microscopy (EM) was used to determine the structure of the human ATR-ATRIP complex.
• Atomic model building was performed for the C-terminal catalytic core of ATR.

Main Results:

• The ATR-ATRIP complex adopts a hollow "heart" shape with two ATR monomers in distinct conformations.
• ATRIP, with its 14 HEAT repeats, locks the ATR monomers, facilitating complex formation.
• The catalytic pockets of ATR are accessible, suggesting unimpeded substrate binding.

Conclusions:

• The study provides unprecedented structural insights into the ATR-ATRIP complex.
• This structural framework aids in understanding ATR-mediated DNA repair pathways and developing targeted therapeutics.