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Biochemical characterization of Calponin homology domain of human IQGAP1
Author(s) -
Kurella Vinodh Babu,
Lecour Louis F,
Worthylake David K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.681.5
Subject(s) - iqgap1 , calmodulin , calponin , microbiology and biotechnology , calcium binding protein , chemistry , actin , scaffold protein , plasma protein binding , biochemistry , calcium , biology , signal transduction , organic chemistry , enzyme
Human IQGAP1 is a190 kDa molecular scaffold that contains several domains required for interaction with proteins such as F‐actin, calmodulin, Cdc42/Rac1, β‐catenin and E‐cadherin. Calponin homology domain (CHD) is a ~160 amino acid module located in the N terminal region of IQGAP1. The CHD belongs to the type 3 family of CH domain containing proteins such as actin‐binding proteins, calponin and Vav. IQGAP1 localizes to the cell cortex, binds to and crosslinks actin via its CHD. When this activity occurs at cadherin‐based cell‐cell junctions, adhesion is stabilized. Calmodulin a calcium sensor, negatively regulates the interaction of IQGAP1 with its binding partners. Preliminary calorimetric analysis suggests that Ca 2+ /calmodulin but not apo‐calmodulin (calcium fee) binds to the N‐ terminal region of IQGAP1 containing the CHD. The mode of binding is apparently sequential with two calmodulin molecules binding to one IQGAP1 CHD. We have just obtained crystals of this CHD and are currently screening for crystals of a complex between Ca 2+ /calmodulin and CHD. It is expected that these structures will reveal conformational changes in the CHD necessary for complex formation and why Ca 2+ /calmodulin but not apo‐calmodulin binds to the CHD. Louisiana board of regents grant