Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring.

• DOI: 10.1083/jcb.111.3.1089
• Publication Date: 2004-05-15T00:18:20Z
• Authors: J B Gorlin; R Yamin; S Egan; M Stewart; T P Stossel; D J Kwiatkowski; J H Hartwig
• Keywords: Actin-binding protein

Actin-binding protein (ABP-280, nonmuscle filamin) is a ubiquitous dimeric actin cross-linking phosphoprotein of peripheral cytoplasm, where it promotes orthogonal branching filaments and links to membrane glycoproteins. The complete nucleotide sequence human endothelial cell ABP cDNA predicts polypeptide subunit chain 2,647 amino acids, corresponding 280 kD, also the mass derived from physical measurements native protein. actin-binding domain near amino-terminus acid similar other filament binding proteins, including alpha-actinin, beta-spectrin, dystrophin, Dictyostelium abp-120. remaining 90% comprises 24 repeats, each approximately 96 residues long, predicted have stretches beta-sheet secondary structure interspersed with turns. first 15 repeats may substantial intrachain hydrophobic interactions overlap in staggered fashion yield backbone mechanical resilience. Sequence insertions immediately before 16 predict two hinges molecule points rotary-shadowed molecules appear swivel electron micrographs. Both putative hinge regions are susceptible cleavage by proteases second contains site that binds platelet glycoprotein Ib/IX complex. Phosphorylation consensus sequences located or them. Degeneracy within every even-numbered repeat between insertion convert chains account for dimer formation 7 kD at carboxy-terminus. dimers resembles leaf spring. Interchain hold leaves firmly together one end, whereas bonds reinforce arms spring diverge, making sufficiently stiff promote high-angle filaments. large size leaves, their interruption flexible site, facilitate widely dispersed