5DCP

Crystal structure of the human filamin B Ig-like domains 16-17

5DCP の概要

• エントリーDOI: 10.2210/pdb5dcp/pdb
• 分子名称: Filamin-B (2 entities in total)
• 機能のキーワード: cytoskeleton, adhesion, immunoglobulin-like, actin binding protein, structural protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 1: Cytoplasm, cell cortex. Isoform 2: Cytoplasm, cytoskeleton. Isoform 3: Cytoplasm, cytoskeleton. Isoform 6: Cytoplasm, cytoskeleton: O75369
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37498.29

構造登録者

Seppala, J.,Pentikainen, U.,Ylanne, J. (登録日: 2015-08-24, 公開日: 2016-08-24, 最終更新日: 2024-01-10)

主引用文献

Seppala, J.,Bernardi, R.C.,Haataja, T.J.K.,Hellman, M.,Pentikainen, O.T.,Schulten, K.,Permi, P.,Ylanne, J.,Pentikainen, U.
Skeletal Dysplasia Mutations Effect on Human Filamins' Structure and Mechanosensing.
Sci Rep, 7:4218-4218, 2017

PubMed Abstract: Cells' ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered molecular dynamics simulations. The effects of skeletal dysplasia associated mutations of the structure and mechanosensing properties of Filamin were studied by combining various experimental and theoretical techniques. The results showed that Larsen syndrome associated mutations destabilize or even unfold domain 17. Interestingly, those Filamin functions that are mediated via domain 17 interactions with other proteins are not necessarily affected as strongly interacting peptide binding to mutated domain 17 induces at least partial domain folding. Mutation associated to Frontometaphyseal dysplasia, in turn, transforms 16-17 fragment from compact to an elongated form destroying the force-regulated domain pair.

PubMed: 28652603
DOI: 10.1038/s41598-017-04441-x

実験手法

X-RAY DIFFRACTION (2.49 Å)