3J2S

Membrane-bound factor VIII light chain

3J2S の概要

• エントリーDOI: 10.2210/pdb3j2s/pdb
• EMDBエントリー: 5540 5559
• 分子名称: Coagulation factor VIII light chain (1 entity in total)
• 機能のキーワード: blood coagulation, cofactor, factor viii, hemophilia, membrane binding, blood clotting
• 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: 74035.36

構造登録者

Stoilova-Mcphie, S.,Lynch, G.C.,Ludtke, S.,Pettitt, B.M. (登録日: 2012-12-21, 公開日: 2013-08-28, 最終更新日: 2024-11-20)

主引用文献

Stoilova-McPhie, S.,Lynch, G.C.,Ludtke, S.,Pettitt, B.M.
Domain organization of membrane-bound factor VIII.
Biopolymers, 99:448-459, 2013

PubMed Abstract: Factor VIII (FVIII) is the blood coagulation protein which when defective or deficient causes for hemophilia A, a severe hereditary bleeding disorder. Activated FVIII (FVIIIa) is the cofactor to the serine protease factor IXa (FIXa) within the membrane-bound Tenase complex, responsible for amplifying its proteolytic activity more than 100,000 times, necessary for normal clot formation. FVIII is composed of two noncovalently linked peptide chains: a light chain (LC) holding the membrane interaction sites and a heavy chain (HC) holding the main FIXa interaction sites. The interplay between the light and heavy chains (HCs) in the membrane-bound state is critical for the biological efficiency of FVIII. Here, we present our cryo-electron microscopy (EM) and structure analysis studies of human FVIII-LC, when helically assembled onto negatively charged single lipid bilayer nanotubes. The resolved FVIII-LC membrane-bound structure supports aspects of our previously proposed FVIII structure from membrane-bound two-dimensional (2D) crystals, such as only the C2 domain interacts directly with the membrane. The LC is oriented differently in the FVIII membrane-bound helical and 2D crystal structures based on EM data, and the existing X-ray structures. This flexibility of the FVIII-LC domain organization in different states is discussed in the light of the FVIIIa-FIXa complex assembly and function.

PubMed: 23616213
DOI: 10.1002/bip.22199

実験手法

ELECTRON MICROSCOPY (15 Å)