Conformational plasticity of histidine kinases is key for catalysis regulation

TRAJTENBERG, FELIPE; ALBANESI, DANIELA; MARTÍN, MARIANA; ALZARI, PEDRO; DE MENDOZA, DIEGO; BUSCHIAZZO, ALEJANDRO

Salta

Congreso; 3rd Latin American Protein Society Meeting; 2010

Latin American Protein Society

DesK is a membrane-bound histidine kinase (HK) from Bacillus subtilis, able to sense the order of membrane lipids when cells are subjected to cold shock. Although the relevance of sensor HKs in signal transduction is well established, we still do not understand at the molecular level how HKs transduce input signal information to regulate their output catalytic activities. We address this issue by using a combination of structural and biochemical approaches. We determined six crystal structures of DesK’s catalytic core, trapped in three conformational states that correspond to alternate functions of the protein along the signaling pathway1. This is a first report comparing the 3D structures of a single HK in different functional configurations. We observe a remarkable plasticity in the central helical domain. The structural comparison of the different DesK variants indicates that incoming signals induce helix rotations and asymmetric helical bends similar to those reported for other sensing systems. These conformational rearrangements modify the accessible surface of the phosphorylation site and the mobility of the ATP-binding domains, ultimately modulating the protein’s catalytic activities. Structure-based mutagenesis and protein engineering experiments, confirm the importance of coiled-coil rotational/shifting movements in the conserved central phosphotransfer domain, suggesting that similar switching mechanisms could operate in a wide range of sensor HKs.        1. Albanesi D., Martín M., Trajtenberg F., Mansilla M.C., Haouz A., Alzari P.M., de Mendoza D. and Buschiazzo, A. Proc Natl Acad Sci USA, 106,16185-16190 (2009).We acknowledge the support of ANII, ANR, CONICET, HHMI, Institut Pasteur and Institut Pasteur de Montevideo