High-resolution crystal structure of gelsolin domain 2 in complex with the physiological calcium ion

TL;DR

This study presents a high-resolution crystal structure of gelsolin domain 2 bound to calcium, revealing subtle ion-dependent structural differences crucial for understanding hereditary amyloidosis.

Contribution

It provides the first high-resolution structure of wild type G2 with calcium, replacing previous cadmium-bound models, and revises mutation insights accordingly.

Findings

G2 structure with calcium shows subtle differences from cadmium-bound form

Structural insights into mutations linked to amyloidosis

Enhanced understanding of calcium's role in G2 function

Abstract

The second domain of gelsolin (G2) hosts mutations responsible for a hereditary form of amyloidosis. The active form of gelsolin is Ca2+-bound; it is also a dynamic protein, hence structural biologists often rely on the study of the isolated G2. However, the wild type G2 structure that have been used so far in comparative studies is bound to a crystallographic Cd2+, in lieu of the physiological calcium. Here, we report the wild type structure of G2 in complex with Ca2+ highlighting subtle ion-dependent differences. Previous findings on different G2 mutations are also briefly revised in light of these results.