Apo raver1 structure reveals distinct RRM domain orientations

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Raver1 is a multifunctional protein involved in alternative splicing and focal adhesion.
• It interacts with polypyrimidine tract protein (PTB), vinculin, and α-actinin.
• The amino-terminal region of raver1 contains three RNA recognition motif (RRM1-3) domains.

Purpose of the Study:

• To determine the crystal structure of unbound raver1 RRM1-3 domains.
• To understand the structural basis of raver1's interactions and regulation.
• To characterize the apo structure of a three-tandem RRM domain construct.

Main Methods:

• X-ray crystallography to determine the 2 Å resolution structure of unbound raver1 RRM1-3 domains.
• Structural comparison with previously determined complex structures.
• Superposition with other RNA-bound RRM structures.

Main Results:

• The apo structure reveals a sulfate ion disrupting inter-domain interactions between RRM1 and RRM2.
• This disruption causes a significant domain movement (>30°).
• The sulfate ion occupies a site suggesting the raver1 RNA binding site.

Conclusions:

• The apo structure provides insights into raver1's conformational flexibility.
• The findings suggest a mechanism for raver1 regulation through domain movement.
• This study reports the second known structure of a three-tandem RRM domain arrangement.