3T1W

Structure of the four-domain fragment Fn7B89 of oncofetal fibronectin

3T1W の概要

• エントリーDOI: 10.2210/pdb3t1w/pdb
• 関連するPDBエントリー: 1FNF 2FNB 2GEE
• 分子名称: four-domain fibronectin fragment (2 entities in total)
• 機能のキーワード: human fibronectin, fn type-iii domain, oncofetal splice variant, extra-domain b, eiiib, ed-b, angiogenesis, integrin, fibronectin, extracellular matrix, protein binding
• 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: 40967.18

構造登録者

Schiefner, A.,Skerra, A. (登録日: 2011-07-22, 公開日: 2012-03-21, 最終更新日: 2023-09-13)

主引用文献

Schiefner, A.,Gebauer, M.,Skerra, A.
Extra-domain B in oncofetal fibronectin structurally promotes fibrillar head-to-tail dimerization of extracellular matrix protein.
J.Biol.Chem., 287:17578-17588, 2012

PubMed Abstract: The type III extra-domain B (ED-B) is specifically spliced into fibronectin (Fn) during embryogenesis and neoangiogenesis, including many cancers. The x-ray structure of the recombinant four-domain fragment Fn(III)7B89 reveals a tightly associated, extended head-to-tail dimer, which is stabilized via pair-wise shape and charge complementarity. A tendency toward ED-B-dependent dimer formation in solution was supported by size exclusion chromatography and analytical ultracentrifugation. When amending the model with the known three-dimensional structure of the Fn(III)10 domain, its RGD loop as well as the adhesion synergy region in Fn(III)9-10 become displayed on the same face of the dimer; this should allow simultaneous binding of at least two integrins and, thus, receptor clustering on the cell surface and intracellular signaling. Insertion of ED-B appears to stabilize overall head-to-tail dimerization of two separate Fn chains, which, together with alternating homodimer formation via disulfide bridges at the C-terminal Fn tail, should lead to the known macromolecular fibril formation.

PubMed: 22442152
DOI: 10.1074/jbc.M111.303131

実験手法

X-RAY DIFFRACTION (2.4 Å)