Multi-Timescale Dynamics Study of FKBP12 Along the Rapamycin–mTOR Binding Coordinate

Sapienza, Paul J.; Mauldin, Randall V.; Lee, Andrew L.

doi:10.1016/j.jmb.2010.10.037

Cited by 30 publications

(92 citation statements)

References 74 publications

(93 reference statements)

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“…3, C and D). Variation of conformational exchange line broadening with the square of the magnetic field strength is indicative of these conformational transitions occurring in the submillisecond time frame approaching the fast exchange limit (21), as had previously been reported for the ␤ 4 -␤ 5 loop in FKBP12 (43)(44)(45).…”

Section: Structural Analysis Of the Interface Between The ␤ 4 -␤supporting

confidence: 72%

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

LeMaster

Mustafi

Brecher

et al. 2015

Journal of Biological Chemistry

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Section: Structural Analysis Of the Interface Between The ␤ 4 -␤supporting

confidence: 72%

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

LeMaster

Mustafi

Brecher

et al. 2015

Journal of Biological Chemistry

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“…The selectivity for lysine labeling in the E. coli expression system was confirmed by signal intensity analyses using the recombinant human FK506 binding protein, of which the 1 H-15 N HSQC NMR signals have already been assigned (Supplemental Fig. S1) [33][34][35]. All lysine signals in the 1 H-15 N HSQC NMR spectrum of the PLC-δ1 PH domain were assigned on the basis of 1 H-15 N HSQC NMR spectra of the lysine-replaced mutants (Supplemental Fig.…”

Section: Local Environmental Changes In the Plc-δ1 Ph Domain Induced mentioning

confidence: 85%

Intramolecular allosteric interaction in the phospholipase C-δ1 pleckstrin homology domain

Tanio

Nishimura

2013

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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“…In analysing the magnetic-field-dependence of the 15 N R 2 relaxation values for the residues of the β 4 –β 5 loop (Supplementary Figure S3 at http://www.biochemj.org/bj/461/bj4610115add.htm) as well as for those in the β 3a strand and β 3 bulge, the increase in conformational line-broadening is approximately proportional to the square of the magnetic field. This implies that the conformational transition rate(s) is substantially higher than the strength of the spinlock field used in the R 1ρ experiments (1245 Hz at 600 MHz and 1085 Hz at 900 MHz), approaching the fast exchange limit as reported previously for FKBP12 [55–57]. The magnitude of conformational line-broadening depends upon the relative population and rate of interchange between the conformer states as well as on the differential 15 N chemical shifts for these states.…”

Section: Resultsmentioning

confidence: 58%

Differential conformational dynamics in the closely homologous FK506-binding domains of FKBP51 and FKBP52

Mustafi

LeMaster

Hernández

2014

Biochemical Journal

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As co-chaperones of Hsp90 (heat-shock protein 90), FKBP51 (FK506-binding protein of 51 kDa) and FKBP52 (FK506-binding protein of 52 kDa) act as antagonists in regulating the hormone affinity and nuclear transport of steroid receptor complexes. Exchange of Leu119 in FKBP51 for Pro119 in FKBP52 has been shown to largely reverse the steroid receptor activities of FKBP51 and FKBP52. To examine whether differences in conformational dynamics/plasticity might correlate with changes in the reported receptor activities, 15N-NMR relaxation measurements were carried out on the N-terminal FKBP domains of FKBP51 and FKBP52 as well as their residue-swapped variants. Both proteins exhibit a similar pattern of motion in the picosecond–nanosecond timeframe as well as a small degree of 15N line-broadening, indicative of motion in the microsecond–millisecond timeframe, in the β3a strand of the central sheet. Only the FKBP51 domain exhibits much larger line-broadening in the adjacent β3 bulge (40′s loop of FKBP12) and throughout the long β4–β5 loop (80′s loop of FKBP12). The L119P mutation at the tip of the β4–β5 loop completely suppressed the line-broadening in this loop while partially suppressing the line-broadening in the neighbouring β2 and β3a strands. The complementary P119L and P119L/P124S variants of FKBP52 yielded similar patterns of line-broadening for the β4–β5 loop as that for FKBP51, although only 20% and 60% as intense respectively. However, despite the close structural similarity in the packing interactions between the β4–β5 loop and the β3a strand for FKBP51 and FKBP52, the line-broadening in the β3a strand is unaffected by the P119L or P119L/P124S mutations in FKBP52.

show abstract

Multi-Timescale Dynamics Study of FKBP12 Along the Rapamycin–mTOR Binding Coordinate

Cited by 30 publications

References 74 publications

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

Intramolecular allosteric interaction in the phospholipase C-δ1 pleckstrin homology domain

Differential conformational dynamics in the closely homologous FK506-binding domains of FKBP51 and FKBP52

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