2bp3: Difference between revisions
No edit summary |
No edit summary |
||
| Line 6: | Line 6: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known diseases associated with this structure: Bernard-Soulier syndrome, type A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], Frontometaphyseal dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Heterotopia, periventricular OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Heterotopia, periventricular nodular, with frontometaphyseal dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Heterotopia, periventricular, ED variant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Melnick-Needles syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], Otopalatodigital syndrome, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Otopalatodigital syndrome, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], von Willebrand disease, platelet-type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]] | |||
==About this Structure== | ==About this Structure== | ||
| Line 21: | Line 24: | ||
[[Category: cytoskeleton]] | [[Category: cytoskeleton]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:04:44 2007'' | ||
Revision as of 21:58, 12 November 2007
|
CRYSTAL STRUCTURE OF FILAMIN A DOMAIN 17 AND GPIB ALPHA CYTOPLASMIC DOMAIN COMPLEX
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Bernard-Soulier syndrome, type A OMIM:[606672], Frontometaphyseal dysplasia OMIM:[300017], Heterotopia, periventricular OMIM:[300017], Heterotopia, periventricular nodular, with frontometaphyseal dysplasia OMIM:[300017], Heterotopia, periventricular, ED variant OMIM:[300017], Melnick-Needles syndrome OMIM:[300017], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[606672], Otopalatodigital syndrome, type I OMIM:[300017], Otopalatodigital syndrome, type II OMIM:[300017], von Willebrand disease, platelet-type OMIM:[606672]
About this StructureAbout this Structure
2BP3 is a Protein complex structure of sequences from Homo sapiens with GOL as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
The structure of the GPIb-filamin A complex., Nakamura F, Pudas R, Heikkinen O, Permi P, Kilpelainen I, Munday AD, Hartwig JH, Stossel TP, Ylanne J, Blood. 2006 Mar 1;107(5):1925-32. Epub 2005 Nov 17. PMID:16293600
Page seeded by OCA on Mon Nov 12 21:04:44 2007