Fig. 5: Overview and proposed structural organization of αB-crystallin in fibrillar and globular states.

a Illustration depicting the αB-crystallin ACD dimer building block (blue) that establishes two hydrophobic IXI-motif binding grooves and a putative NTD binding groove at the dimer interface. The NTD (gray) comprises two conserved regions, the NT-IXI motif (dark gray box) and a conserved hydrophobic region (light gray box). The CTD (red) contains the conserved CT-IXI motif (orange box). b When the NT-IXI is ablated (αB-AXA), the CT-IXI can form persistent and stable interactions with the IXI binding grooves in the ACD, promoting elongated fibril assembly. In this state, the NTD is buried within the interior cavity of the assembly. The NTD binding groove of the ACD is occupied and is presumed to correspond to the conserved region of the NTD. Upon heating the αB-AXA construct from 25 °C to 37−42 °C, the structure transitions into a globular state resembling wild-type αB-crystallin (αB-WT). This transformation is proposed to result from thermal energy causing rapid exchange of the CT-IXI with the ACD IXI-binding groove, mimicking the exchange mechanism proposed in αB-WT, where both the CT-IXI and NT-IXI undergo competition exchange for a limited number of binding grooves in the ACD.