The structure of the GPIb-filamin A complex.

Abstract:

:Filamin A (FLNa), a dimeric actin cross-linking and scaffold protein with numerous intracellular binding partners, anchors the platelet adhesion glycoprotein (GP) Ib-IX-V receptor to actin cytoskeleton. We mapped the GPIbalpha binding site to a single domain of FLNa and resolved the structure of this domain and its interaction complex with the corresponding GPIbalpha cytoplasmic domain. This is the first atomic structure of this class of membrane glycoprotein-cytoskeleton connection. GPIbalpha binds in a groove formed between the C and D beta strands of FLNa domain 17. The interaction is strikingly similar to that between the beta7 integrin tail and a different FLNa domain, potentially defining a conserved motif for FLNa binding. Nevertheless, the structures also reveal specificity of the interfaces, which explains different regulatory mechanisms. To verify the topology of GPIb-FLNa interaction we also purified the native complex from platelets and showed that GPIb interacts with the C-terminus of FLNa, which is in accordance with our biochemical and structural data.

journal_name

Blood

journal_title

Blood

authors

Nakamura F,Pudas R,Heikkinen O,Permi P,Kilpeläinen I,Munday AD,Hartwig JH,Stossel TP,Ylänne J

doi

10.1182/blood-2005-10-3964

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

1925-32

issue

5

eissn

0006-4971

issn

1528-0020

pii

2005-10-3964

journal_volume

107

pub_type

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