1qvx: Difference between revisions

Revision as of 15:44, 21 February 2008

SOLUTION STRUCTURE OF THE FAT DOMAIN OF FOCAL ADHESION KINASE

OverviewOverview

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is regulated by integrins. Upon activation, FAK generates signals that modulate crucial cell functions, including cell proliferation, migration, and survival. The C-terminal focal adhesion targeting (FAT) sequence mediates localization of FAK to discrete regions in the cell called focal adhesions. Several binding partners for the FAT domain of FAK have been identified, including paxillin. We have determined the solution structure of the avian FAT domain in complex with a peptide mimicking the LD2 motif of paxillin by NMR spectroscopy. The FAT domain retains a similar fold to that found in the unliganded form when complexed to the paxillin-derived LD2 peptide, an antiparallel four-helix bundle. However, noticeable conformational changes were observed upon the LD2 peptide binding, especially the position of helix 4. Multiple lines of evidence, including the results obtained from isothermal titration calorimetry, intermolecular nuclear Overhauser effects, mutagenesis, and protection from paramagnetic line broadening, support the existence of two distinct paxillin-binding sites on the opposite faces of the FAT domain. The structure of the FAT domain-LD2 complex was modeled using the program HADDOCK based on our solution structure of the LD2-bound FAT domain and mutagenesis data. Our model of the FAT domain-LD2 complex provides insight into the molecular basis of FAK-paxillin binding interactions, which will aid in understanding the role of paxillin in FAK targeting and signaling.

About this StructureAbout this Structure

1QVX is a Single protein structure of sequence from Gallus gallus. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

ReferenceReference

NMR solution structure of the focal adhesion targeting domain of focal adhesion kinase in complex with a paxillin LD peptide: evidence for a two-site binding model., Gao G, Prutzman KC, King ML, Scheswohl DM, DeRose EF, London RE, Schaller MD, Campbell SL, J Biol Chem. 2004 Feb 27;279(9):8441-51. Epub 2003 Dec 7. PMID:14662767

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 '''SOLUTION STRUCTURE OF THE FAT DOMAIN OF FOCAL ADHESION KINASE'''<br />
 ==Overview==
-Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is, regulated by integrins. Upon activation, FAK generates signals that, modulate crucial cell functions, including cell proliferation, migration, and survival. The C-terminal focal adhesion targeting (FAT) sequence, mediates localization of FAK to discrete regions in the cell called focal, adhesions. Several binding partners for the FAT domain of FAK have been, identified, including paxillin. We have determined the solution structure, of the avian FAT domain in complex with a peptide mimicking the LD2 motif, of paxillin by NMR spectroscopy. The FAT domain retains a similar fold to, that found in the unliganded form when complexed to the paxillin-derived, LD2 peptide, an antiparallel four-helix bundle. However, noticeable, conformational changes were observed upon the LD2 peptide binding, especially the position of helix 4. Multiple lines of evidence, including, the results obtained from isothermal titration calorimetry, intermolecular, nuclear Overhauser effects, mutagenesis, and protection from paramagnetic, line broadening, support the existence of two distinct paxillin-binding, sites on the opposite faces of the FAT domain. The structure of the FAT, domain-LD2 complex was modeled using the program HADDOCK based on our, solution structure of the LD2-bound FAT domain and mutagenesis data. Our, model of the FAT domain-LD2 complex provides insight into the molecular, basis of FAK-paxillin binding interactions, which will aid in, understanding the role of paxillin in FAK targeting and signaling.
+Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is regulated by integrins. Upon activation, FAK generates signals that modulate crucial cell functions, including cell proliferation, migration, and survival. The C-terminal focal adhesion targeting (FAT) sequence mediates localization of FAK to discrete regions in the cell called focal adhesions. Several binding partners for the FAT domain of FAK have been identified, including paxillin. We have determined the solution structure of the avian FAT domain in complex with a peptide mimicking the LD2 motif of paxillin by NMR spectroscopy. The FAT domain retains a similar fold to that found in the unliganded form when complexed to the paxillin-derived LD2 peptide, an antiparallel four-helix bundle. However, noticeable conformational changes were observed upon the LD2 peptide binding, especially the position of helix 4. Multiple lines of evidence, including the results obtained from isothermal titration calorimetry, intermolecular nuclear Overhauser effects, mutagenesis, and protection from paramagnetic line broadening, support the existence of two distinct paxillin-binding sites on the opposite faces of the FAT domain. The structure of the FAT domain-LD2 complex was modeled using the program HADDOCK based on our solution structure of the LD2-bound FAT domain and mutagenesis data. Our model of the FAT domain-LD2 complex provides insight into the molecular basis of FAK-paxillin binding interactions, which will aid in understanding the role of paxillin in FAK targeting and signaling.
 ==About this Structure==
-QVX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QVX OCA].
+QVX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QVX OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Transferase]]
-[[Category: Campbell, S.L.]]
+[[Category: Campbell, S L.]]
-[[Category: DeRose, E.F.]]
+[[Category: DeRose, E F.]]
 [[Category: Gao, G.]]
-[[Category: King, M.L.]]
+[[Category: King, M L.]]
-[[Category: London, R.E.]]
+[[Category: London, R E.]]
-[[Category: Prutzman, K.C.]]
+[[Category: Prutzman, K C.]]
-[[Category: Schaller, M.D.]]
+[[Category: Schaller, M D.]]
 [[Category: fak]]
 [[Category: fat]]
@@ Line 28: / Line 28: @@
 [[Category: nmr]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:02:46 2007''
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