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Conformational diversity in poly-HAMP arrays and its implications for signal transduction
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DOI：10.1002/pro.70743.png)
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Abstract
En 中文
Prokaryotic transmembrane receptors are built around a helical coiled-coil backbone, with sensory, modulatory, and effector domains arranged along its length. The modulatory HAMP domain forms a parallel four-helix coiled coil integrated into this backbone, typically connecting transmembrane segments with downstream cytosolic domains. In many systems, HAMP domains transduce signals through axial rotation of their helices; however, it is not clear how broadly applicable this mechanism is. Here, we describe two families of soluble chemoreceptors and sensory kinases that contain long arrays of concatenated HAMP domains, which we term poly-HAMP. Although these poly-HAMP arrays evolved independently, both families share sequence features consistent with convergence on a similar functional system. We determined the crystal structures of 4-HAMP and 6-HAMP segments from the poly-HAMP array of histidine kinase AskA of Myxococcus xanthus, revealing unusually close packing between adjacent domains and conformational patterns compatible with the rotational signaling model. To define the broader conformational landscape, we computed AlphaFold2 models for over 200 chemoreceptor- and kinase-associated arrays. The models were consistent with the AskA structures, yet revealed distinct preferences: chemoreceptor arrays were predicted to adopt stable conformations, whereas kinase arrays more frequently adopted potentially less favorable conformations. When modeled in isolation from neighboring domains, HAMP domains from kinase arrays adopted alternative conformations related to their array-embedded forms by axial helix rotation. Taken together, our results suggest that, despite their independent origins, HAMP-containing systems including poly-HAMP arrays and canonical single-HAMP receptors may share a conserved mode of conformational plasticity involving axial helix rotation.
Keywords:
AlphaFold2
class III histidine kinases
coiled coils
conformational switching
HAMP domain
poly-HAMP arrays
signal transduction
x-ray crystallography
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