2KFU

PknB-phosphorylated Rv1827

2KFU の概要

• エントリーDOI: 10.2210/pdb2kfu/pdb
• NMR情報: BMRB: 16248
• 分子名称: Rv1827 pThr 22 (1 entity in total)
• 機能のキーワード: fha domain, mycobacterium tuberculosis, phosphorylation, intramolecular interaction, glutamate metabolism, phosphoprotein, protein binding
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17313.74

構造登録者

Smerdon, S.J.,Nott, T.J.,Kelly, G. (登録日: 2009-02-27, 公開日: 2009-06-16, 最終更新日: 2024-11-06)

主引用文献

Nott, T.J.,Kelly, G.,Stach, L.,Li, J.,Westcott, S.,Patel, D.,Hunt, D.M.,Howell, S.,Buxton, R.S.,O'Hare, H.M.,Smerdon, S.J.
An intramolecular switch regulates phosphoindependent FHA domain interactions in Mycobacterium tuberculosis.
Sci.Signal., 2:ra12-ra12, 2009

PubMed Abstract: Forkhead-associated (FHA) domains have gained considerable prominence as ubiquitous phosphothreonine-dependent binding modules; however, their precise roles in serine and threonine kinase (STK) pathways and mechanisms of regulation remain unclear. From experiments with Rv1827, an FHA domain-containing protein from Mycobacterium tuberculosis, we derived a complete molecular description of an FHA-mediated STK signaling process. First, binding of the FHA domain to each of three metabolic enzyme complexes regulated their catalytic activities but did not require priming phosphorylation. However, phosphorylation of a threonine residue within a conserved amino-terminal motif of Rv1827 triggered its intramolecular association with the FHA domain of Rv1827, thus blocking its interactions with each of the three enzymes. The solution structure of this inactivated form and further mutagenic studies showed how a previously unidentified intramolecular phosphoswitch blocked the access of the target enzymes to a common FHA interaction surface and how this shared surface accommodated three functionally related, but structurally diverse, binding partners. Thus, our data reveal an unsuspected versatility in the FHA domain that allows for the transformation of multiple kinase inputs into various downstream regulatory signals.

PubMed: 19318624
DOI: 10.1126/scisignal.2000212

実験手法

SOLUTION NMR