Factor VIII C1 domain spikes 2092–2093 and 2158–2159 comprise regions that modulate cofactor function and cellular uptake

E Bloem, M van den Biggelaar, A Wroblewska… - Journal of Biological …, 2013 - ASBMB
The C1 domain of factor VIII (FVIII) has been implicated in binding to multiple constituents,
including phospholipids, von Willebrand factor, and low-density lipoprotein receptor-related
protein (LRP). We have previously described a human monoclonal antibody called KM33
that blocks these interactions as well as cellular uptake by LRP-expressing cells. To
unambiguously identify the apparent" hot spot" on FVIII to which this antibody binds, we
have employed hydrogen-deuterium exchange mass spectrometry. The results showed that …
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