Crystal structure of kindlin-2 PH domain reveals a conformational transition for its membrane anchoring and regulation of integrin activation
Protein & Cell
;
(12): 434-440, 2012.
Article
in English
| WPRIM
| ID: wpr-757260
ABSTRACT
Kindlin-2 belongs to a subfamily of FERM domain containing proteins, which plays key roles in activating integrin transmembrane receptors and mediating cell adhesion. Compared to conventional FERM domains, kindlin-2 FERM contains an inserted pleckstrin homology (PH) domain that specifically binds to phosphatidylinositol (3,4,5) trisphosphate (PIP3) and regulates the kindlin-2 function. We have determined the crystal structure of kindlin-2 PH domain at 1.9 Å resolution, which reveals a conserved PH domain fold with a highly charged and open binding pocket for PIP3 head group. Structural comparison with a previously reported solution structure of kindlin-2 PH domain bound to PIP3 head group reveals that upon PIP3 insertion, there is a significant conformational change of both the highly positively charged loop at the entry of the PIP3 binding pocket and the entire β barrel of the PH domain. We propose that such "induced-fit" type change is crucial for the tight binding of PIP3 to anchor kindlin-2 onto the membrane surface, thereby promoting its binding to integrins. Our results provide important structural insight into kindlin-2-mediated membrane anchoring and integrin activation.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Protein Conformation
/
Models, Molecular
/
Integrins
/
Chemistry
/
Crystallography, X-Ray
/
Cytoskeletal Proteins
/
Membrane Proteins
/
Metabolism
/
Muscle Proteins
/
Neoplasm Proteins
Limits:
Animals
/
Humans
Language:
English
Journal:
Protein & Cell
Year:
2012
Type:
Article
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