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6iuh

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Revision as of 08:15, 24 April 2019

Crystal structure of GIT1 PBD domain in complex with Liprin-alpha2

Structural highlights

6iuh is a 4 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Git1 (Buffalo rat), PPFIA2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GIT1_RAT] GTPase-activating protein for the ADP ribosylation factor family. May serve as a scaffold to bring together molecules to form signaling modules controlling vesicle trafficking, adhesion and cytoskeletal organization. Increases the speed of cell migration, as well as the size and rate of formation of protrusions, possibly by targeting PAK1 to adhesions and the leading edge of lamellipodia. Sequesters inactive non-tyrosine-phosphorylated paxillin in cytoplasmic complexes. [LIPA2_HUMAN] Alters PTPRF cellular localization and induces PTPRF clustering. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.^[1]

Publication Abstract from PubMed

Focal adhesions (FAs) are specialized sites where intracellular cytoskeleton elements connect to the extracellular matrix and thereby control cell motility. FA assembly depends on various scaffold proteins, including the G protein-coupled receptor kinase-interacting protein 1 (GIT1), paxillin and liprin-alpha. Although liprin-alpha and paxillin are known to competitively interact with GIT1, the molecular basis governing these interactions remains elusive. To uncover the underlying mechanisms of how GIT1 is involved in FAs assembly by alternatively binding to liprin-alpha and paxillin, here we solved the crystal structures of GIT1 in complex with liprin-alpha and paxillin at 1.8 A and 2.6 A resolutions, respectively. These structures revealed that the paxillin-binding domain (PBD) of GIT1 employs distinct binding modes to recognize a single alpha helix of liprin-alpha and the LD4 motif of paxillin. Structure-based design of protein variants produced two binding-deficient GIT1 variants; specifically, these variants lost the ability to interact with liprin-alpha only or with both liprin-alpha and paxillin. Expressing the GIT1 variants in COS7 cells, we discovered that the two PBD-meditated interactions play different roles in either recruiting GIT1 to FA or facilitating FA assembly. Additionally, we demonstrate that, unlike for the known binding mode of the FAT domain to LD motifs, the PBD of GIT1 uses different surface patches to achieve high selectivity in LD-motif recognition. In summary, our results have uncovered the mechanisms by which GIT1's PBD recognizes cognate paxillin and liprin-alpha structures, information we anticipate will be useful for future investigations of GIT1-protein interactions in cells.

Structural basis of the target-binding mode of the G protein-coupled receptor kinase-interacting protein in the regulation of focal adhesion dynamics.,Liang M, Xie X, Pan J, Jin G, Yu C, Wei Z J Biol Chem. 2019 Feb 8. pii: RA118.006915. doi: 10.1074/jbc.RA118.006915. PMID:30737283^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Serra-Pages C, Medley QG, Tang M, Hart A, Streuli M. Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J Biol Chem. 1998 Jun 19;273(25):15611-20. PMID:9624153
↑ Liang M, Xie X, Pan J, Jin G, Yu C, Wei Z. Structural basis of the target-binding mode of the G protein-coupled receptor kinase-interacting protein in the regulation of focal adhesion dynamics. J Biol Chem. 2019 Feb 8. pii: RA118.006915. doi: 10.1074/jbc.RA118.006915. PMID:30737283 doi:http://dx.doi.org/10.1074/jbc.RA118.006915

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6iuh"

@@ Line 1: / Line 1: @@
 ==Crystal structure of GIT1 PBD domain in complex with Liprin-alpha2==
-<StructureSection load='6iuh' size='340' side='right' caption='[[6iuh]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='6iuh' size='340' side='right'caption='[[6iuh]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6iuh]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IUH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IUH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6iuh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IUH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IUH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Git1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), PPFIA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6iuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iuh OCA], [http://pdbe.org/6iuh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iuh RCSB], [http://www.ebi.ac.uk/pdbsum/6iuh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iuh ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Liang, M]]
 [[Category: Wei, Z]]
 [[Category: Complex]]
 [[Category: Protein binding]]

6iuh

From Proteopedia

Revision as of 08:15, 24 April 2019

Crystal structure of GIT1 PBD domain in complex with Liprin-alpha2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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