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Histidine Kinase CheA: You Spin Me ′Round
Author(s) -
Chou Chris,
Martyr Richard,
Barila Diana,
Chaney Michael,
Drewes Jake,
Hak Iain,
Harroun Haleakala,
Kamenides Theodore,
Lippard Maya,
Martyr Cara,
Merrill Jack,
Mugunga Tol,
Neuhard Zoe,
Real Sophia,
Swope Danielle,
Wilkinson Tyler,
Falke Joseph J
Publication year - 2017
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.31.1_supplement.lb260
Subject(s) - autophosphorylation , histidine kinase , histidine , kinase , biochemistry , protein kinase domain , biophysics , periplasmic space , biology , chemistry , microbiology and biotechnology , protein kinase a , enzyme , escherichia coli , gene , mutant
Annually, 600 cases of necrotizing fasciitis, caused by wound seeking bacteria, are documented in the United States. One in four patients who contract this infection die. Researchers seek a method to block bacterial chemosensing, to prevent wound seeking and infection. Histidine kinase CheA (CheA) is central to chemosensing and chemotaxis. CheA is coupled to a transmembrane methyl‐accepting chemoreceptor, which detects attractants and repellants. CheA is a homodimer and each subunit contains five domains: substrate (P1), CheY binding (P2), dimerization (P3), kinase (P4), and regulation (P5). P1 contains the histidine residue that is the site of autophosphorylation. Attractant or repellent binding to the chemoreceptor inhibits or activates autophosphorylation of the histidine, respectively. Following autophosphorylation the phosphate is transferred, yielding phospho‐CheY. Low phospho‐CheY maintains the current swimming direction, while high phospho‐CheY causes the bacteria to stop and reorient. Hydrophobic dimerization interfaces in CheA create an energy barrier to dissociation of the subunits, ensuring a stable dimer for proper regulatory and kinase functions. The dimerization domain is linked to the kinase domain by a highly conserved flexible link. Due to their 3D orientation, the kinase and regulatory domains of the monomer do not interact, rather they interact with the complementary monomer. The kinase domain contains a deep cleft that is the ATP binding site. The Longmont High School SMART (Students Modeling a Research Topic) Team modeled histidine kinase CheA using 3D printing technology to investigate structure‐function relationships. By understanding the way that bacteria move, we can more effectively fight pathogenic bacteria.