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Updated: Aug 30, 2026

Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes
Published on: June 3, 2014
LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII
M A Cunningham1, S W Pipe, B Zhang
1Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA.
Abstract:
Combined deficiency of both coagulation factors (F)V and VIII is a rare autosomal recessive bleeding disorder caused by null expression of LMAN1 (previously termed ERGIC-53) in a majority of affected individuals. Previously, a requirement for a functional LMAN1 cycling pathway between the ER and Golgi was demonstrated for efficient secretion of FV and FVIII (Moussalli et al. J Biol Chem 1999; 274: 32569), however, the molecular nature of the interaction between LMAN1 and its cargo was not characterized. Using coimmunoprecipitation of LMAN1 and FVIII from transfected HeLa and COS-1 cells, we demonstrate an interaction between LMAN1 and FVIII in vivo. The interaction was mediated via high mannose-containing asparagine-linked oligosaccharides that are densely situated within the B domain of FVIII, as well as protein-protein interactions. These results are interpreted based on the recent determination of the crystal structure of the carbohydrate recognition domain of LMAN1.
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