5XPY

Structural basis of kindlin-mediated integrin recognition and activation

5XPY の概要

• エントリーDOI: 10.2210/pdb5xpy/pdb
• 分子名称: Fermitin family homolog 2, ACETATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: integrin binding, multi-domain containing protein, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cytoplasm : Q8CIB5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55470.63

構造登録者

Li, H.,Yang, H.,Sun, K.,Zhang, Z.,Yu, C.,Wei, Z. (登録日: 2017-06-05, 公開日: 2017-07-26, 最終更新日: 2023-11-22)

主引用文献

Li, H.,Deng, Y.,Sun, K.,Yang, H.,Liu, J.,Wang, M.,Zhang, Z.,Lin, J.,Wu, C.,Wei, Z.,Yu, C.
Structural basis of kindlin-mediated integrin recognition and activation
Proc. Natl. Acad. Sci. U.S.A., 114:9349-9354, 2017

PubMed Abstract: Kindlins and talins are integrin-binding proteins that are critically involved in integrin activation, an essential process for many fundamental cellular activities including cell-matrix adhesion, migration, and proliferation. As FERM-domain-containing proteins, talins and kindlins, respectively, bind different regions of β-integrin cytoplasmic tails. However, compared with the extensively studied talin, little is known about how kindlins specifically interact with integrins and synergistically enhance their activation by talins. Here, we determined crystal structures of kindlin2 in the apo-form and the β1- and β3-integrin bound forms. The apo-structure shows an overall architecture distinct from talins. The complex structures reveal a unique integrin recognition mode of kindlins, which combines two binding motifs to provide specificity that is essential for integrin activation and signaling. Strikingly, our structures uncover an unexpected dimer formation of kindlins. Interrupting dimer formation impairs kindlin-mediated integrin activation. Collectively, the structural, biochemical, and cellular results provide mechanistic explanations that account for the effects of kindlins on integrin activation as well as for how kindlin mutations found in patients with Kindler syndrome and leukocyte-adhesion deficiency may impact integrin-mediated processes.

PubMed: 28739949
DOI: 10.1073/pnas.1703064114

実験手法

X-RAY DIFFRACTION (2.099 Å)