9FJW

Solution NMR structure of a peptide encompassing residues 2-36 of the human formin INF2

9FJW の概要

• エントリーDOI: 10.2210/pdb9fjw/pdb
• NMR情報: BMRB: 51408
• 分子名称: Inverted formin-2 (1 entity in total)
• 機能のキーワード: formins, actin, microtubules, inherited disease, cell adhesion
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3801.11

構造登録者

Jimenez, M.A.,Comas, L.,Labat-de-Hoz, L.,Correas, I.,Alonso, M.A. (登録日: 2024-05-31, 公開日: 2024-09-11)

主引用文献

Labat-de-Hoz, L.,Comas, L.,Rubio-Ramos, A.,Casares-Arias, J.,Fernandez-Martin, L.,Pantoja-Uceda, D.,Martin, M.T.,Kremer, L.,Jimenez, M.A.,Correas, I.,Alonso, M.A.
Structure and function of the N-terminal extension of the formin INF2.
Cell Mol Life Sci, 79:571-, 2022

PubMed Abstract: In INF2-a formin linked to inherited renal and neurological disease in humans-the DID is preceded by a short N-terminal extension of unknown structure and function. INF2 activation is achieved by Ca-dependent association of calmodulin (CaM). Here, we show that the N-terminal extension of INF2 is organized into two α-helices, the first of which is necessary to maintain the perinuclear F-actin ring and normal cytosolic F-actin content. Biochemical assays indicated that this helix interacts directly with CaM and contains the sole CaM-binding site (CaMBS) detected in INF2. The residues W11, L14 and L18 of INF2, arranged as a 1-4-8 motif, were identified as the most important residues for the binding, W11 being the most critical of the three. This motif is conserved in vertebrate INF2 and in the human population. NMR and biochemical analyses revealed that CaM interacts directly through its C-terminal lobe with the INF2 CaMBS. Unlike control cells, INF2 KO cells lacked the perinuclear F-actin ring, had little cytosolic F-actin content, did not respond to increased Ca concentrations by making more F-actin, and maintained the transcriptional cofactor MRTF predominantly in the cytoplasm. Whereas expression of intact INF2 restored all these defects, INF2 with inactivated CaMBS did not. Our study reveals the structure of the N-terminal extension, its interaction with Ca/CaM, and its function in INF2 activation.

PubMed: 36306014
DOI: 10.1016/j.jmb.2015.09.014

実験手法

SOLUTION NMR