4F7H

The crystal structure of kindlin-2 pleckstrin homology domain in free form

Summary for 4F7H

• Entry DOI: 10.2210/pdb4f7h/pdb
• Related: 2LKO
• Descriptor: Fermitin family homolog 2, S,R MESO-TARTARIC ACID (3 entities in total)
• Functional Keywords: beta-barrel, membrane binding, integrin activation, cytoplasmic membrane, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cell cortex: Q96AC1
• Total number of polymer chains: 1
• Total formula weight: 19733.31

Authors

Liu, Y.,Zhu, Y.,Qin, J.,Ye, S.,Zhang, R. (deposition date: 2012-05-16, release date: 2012-06-13, Last modification date: 2023-09-13)

Primary citation

Liu, Y.,Zhu, Y.,Ye, S.,Zhang, R.
Crystal structure of kindlin-2 PH domain reveals a conformational transition for its membrane anchoring and regulation of integrin activation.
Protein Cell, 3:434-440, 2012

PubMed 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.

PubMed: 22653426
DOI: 10.1007/s13238-012-2046-1

Experimental method

X-RAY DIFFRACTION (1.9 Å)