1Y19

Structural basis for phosphatidylinositol phosphate kinase type I-gamma binding to talin at focal adhesions

Summary for 1Y19

• Entry DOI: 10.2210/pdb1y19/pdb
• Related: 1MIX 1MIZ 1MK7 1MK9
• Descriptor: Phosphatidylinositol-4-phosphate 5-kinase, type 1 gamma, Talin 1 (3 entities in total)
• Functional Keywords: focal adhesion; ferm domain; cytoskeleton; npxy motif; ptb domain, structural protein, signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: O70161; Cell projection, ruffle membrane ; Peripheral membrane protein ; Cytoplasmic side : P26039
• Total number of polymer chains: 12
• Total formula weight: 149962.76

Authors

de Pereda, J.M.,Wegener, K.,Santelli, E.,Bate, N.,Ginsberg, M.H.,Critchley, D.R.,Campbell, I.D.,Liddington, R.C. (deposition date: 2004-11-17, release date: 2005-01-04, Last modification date: 2024-11-06)

Primary citation

de Pereda, J.M.,Wegener, K.,Santelli, E.,Bate, N.,Ginsberg, M.H.,Critchley, D.R.,Campbell, I.D.,Liddington, R.C.
Structural bases for phosphatidylinositol phosphate kinase type I-gamma binding to talin at focal adhesions
J.Biol.Chem., 280:8381-8386, 2005

PubMed Abstract: The cytoskeletal protein talin binds to a short C-terminal sequence in phosphatidylinositol phosphate kinase type Igamma (PIPKIgamma), activating the enzyme and promoting the local production of phosphatidylinositol 4,5 bisphosphate, which regulates focal adhesion dynamics as well as clathrin-mediated endocytosis in neuronal cells. Here we show by crystallographic, NMR, and calorimetric analysis that the phosphotyrosine binding (PTB)-like domain of talin engages the PIPKIgamma C terminus in a mode very similar to that of integrin binding. However, PIPKIgamma binds in the canonical PTB-peptide mode with an SPLH motif replacing the classic NPXY motif. The tighter packing of the SPLH motif against the hydrophobic core of talin may explain the stronger binding of PIPKIgamma. Two tyrosine residues flanking the SPLH motif (Tyr-644 and Tyr-649) have been implicated in the regulation of talin binding. We show that phosphorylation at Tyr-644, a Src phosphorylation site in vivo, has little effect on the binding mode or strength, which is consistent with modeling studies in which the phosphotyrosine makes surface-exposed salt bridges, and we suggest that its strong activating effect arises from the release of autoinhibitory restraints in the full-length PIPKIgamma. Modeling studies suggest that phosphorylation of Tyr-649 will likewise have little effect on talin binding, whereas phosphorylation of the SPLH serine is predicted to be strongly disruptive. Our data are consistent with the proposal that Src activity promotes a switch from integrin binding to PIPKIgamma binding that regulates focal adhesion turnover.

PubMed: 15623515
DOI: 10.1074/jbc.M413180200

Experimental method

X-RAY DIFFRACTION (2.6 Å)