9fjw

Solution NMR structure of a peptide encompassing residues 2-36 of the human formin INF2Solution NMR structure of a peptide encompassing residues 2-36 of the human formin INF2

Structural highlights 9fjw is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease INF2_HUMAN Autosomal dominant intermediate Charcot-Marie-Tooth disease type E;Genetic steroid-resistant nephrotic syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Function INF2_HUMAN Severs actin filaments and accelerates their polymerization and depolymerization. Publication Abstract from PubMed 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(2+)-dependent association of calmodulin (CaM). Here, we show that the N-terminal extension of INF2 is organized into two alpha-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(2+) 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(2+)/CaM, and its function in INF2 activation. Structure and function of the N-terminal extension of the formin INF2.,Labat-de-Hoz L, Comas L, Rubio-Ramos A, Casares-Arias J, Fernandez-Martin L, Pantoja-Uceda D, Martin MT, Kremer L, Jimenez MA, Correas I, Alonso MA Cell Mol Life Sci. 2022 Oct 28;79(11):571. doi: 10.1007/s00018-022-04581-y. PMID:36306014 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 9fjw Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image