3J2S: Membrane-bound Factor Viii Light Chain

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. (c) 2013 Wiley Periodicals, Inc. Biopolymers 99: 448-459, 2013.
PDB ID: 3J2SDownload
MMDB ID: 112924
PDB Deposition Date: 2012/12/21
Updated in MMDB: 2013/08
Experimental Method:
electron microscopy
Resolution: 15  Å
Source Organism:
Similar Structures:
Biological Unit for 3J2S: monomeric; determined by author
Molecular Components in 3J2S
Label Count Molecule
Protein (1 molecule)
Coagulation Factor Viii Light Chain(Gene symbol: F8)
Molecule annotation
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Citing MMDB