Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant

J. Evenäs, A. Malmendal, M. Akke

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: Calmodulin is a ubiquitous Ca2+-activated regulator of cellular processes in eukaryotes. The structures of the Ca2+-free (apo) and Ca2+-loaded states of calmodulin have revealed that Ca2+binding is associated with a transition in each of the two domains from a closed to an open conformation that is central to target recognition. However, little is known about the dynamics of this conformational switch. Results: The dynamics of the transition between closed and open conformations in the Ca2+-loaded state of the E140Q mutant of the calmodulin C-terminal domain were characterized under equilibrium conditions. The exchange time constants ($ex) measured for 42 residues range from 13 to 46 $s, with a mean of 21 \ 3 $s. The results suggest that $exvaries significantly between different groups of residues and that residues with similar values exhibit spatial proximity in the structures of apo and/or Ca2+-saturated wild-type calmodulin. Using data for one of these groups, we obtained an open population of po= 0.50 \ 0.17 and a closed \ open rate constant of ko= (2.7 \ 1.0) \ 104s-1. Conclusions: The conformational exchange dynamics appear to involve locally collective processes that depend on the structural topology. Comparisons with previous results indicate that similar processes occur in the wild-type protein. The measured rates match the estimated Ca2+off rate, suggesting that Ca2+release may be gated by the conformational dynamics. Structural interpretation of estimated chemical shifts suggests a mechanism for ion release.
OriginalsprogEngelsk
TidsskriftWord Structure
Vol/bind9
Udgave nummer3
ISSN1750-1245
DOI
StatusUdgivet - 2001

Emneord

  • Conformational exchange
  • Dynamics
  • NMR
  • Off-resonance rotating-frame N spin relaxation 15

Citer dette

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title = "Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant",
abstract = "Background: Calmodulin is a ubiquitous Ca2+-activated regulator of cellular processes in eukaryotes. The structures of the Ca2+-free (apo) and Ca2+-loaded states of calmodulin have revealed that Ca2+binding is associated with a transition in each of the two domains from a closed to an open conformation that is central to target recognition. However, little is known about the dynamics of this conformational switch. Results: The dynamics of the transition between closed and open conformations in the Ca2+-loaded state of the E140Q mutant of the calmodulin C-terminal domain were characterized under equilibrium conditions. The exchange time constants ($ex) measured for 42 residues range from 13 to 46 $s, with a mean of 21 \ 3 $s. The results suggest that $exvaries significantly between different groups of residues and that residues with similar values exhibit spatial proximity in the structures of apo and/or Ca2+-saturated wild-type calmodulin. Using data for one of these groups, we obtained an open population of po= 0.50 \ 0.17 and a closed \ open rate constant of ko= (2.7 \ 1.0) \ 104s-1. Conclusions: The conformational exchange dynamics appear to involve locally collective processes that depend on the structural topology. Comparisons with previous results indicate that similar processes occur in the wild-type protein. The measured rates match the estimated Ca2+off rate, suggesting that Ca2+release may be gated by the conformational dynamics. Structural interpretation of estimated chemical shifts suggests a mechanism for ion release.",
keywords = "Conformational exchange, Dynamics, NMR, Off-resonance rotating-frame N spin relaxation 15",
author = "J. Even{\"a}s and A. Malmendal and M. Akke",
year = "2001",
doi = "10.1016/S0969-2126(01)00575-5",
language = "English",
volume = "9",
journal = "Word Structure",
issn = "1750-1245",
publisher = "Edinburgh University Press Ltd.",
number = "3",

}

Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant. / Evenäs, J.; Malmendal, A.; Akke, M.

I: Word Structure, Bind 9, Nr. 3, 2001.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant

AU - Evenäs, J.

AU - Malmendal, A.

AU - Akke, M.

PY - 2001

Y1 - 2001

N2 - Background: Calmodulin is a ubiquitous Ca2+-activated regulator of cellular processes in eukaryotes. The structures of the Ca2+-free (apo) and Ca2+-loaded states of calmodulin have revealed that Ca2+binding is associated with a transition in each of the two domains from a closed to an open conformation that is central to target recognition. However, little is known about the dynamics of this conformational switch. Results: The dynamics of the transition between closed and open conformations in the Ca2+-loaded state of the E140Q mutant of the calmodulin C-terminal domain were characterized under equilibrium conditions. The exchange time constants ($ex) measured for 42 residues range from 13 to 46 $s, with a mean of 21 \ 3 $s. The results suggest that $exvaries significantly between different groups of residues and that residues with similar values exhibit spatial proximity in the structures of apo and/or Ca2+-saturated wild-type calmodulin. Using data for one of these groups, we obtained an open population of po= 0.50 \ 0.17 and a closed \ open rate constant of ko= (2.7 \ 1.0) \ 104s-1. Conclusions: The conformational exchange dynamics appear to involve locally collective processes that depend on the structural topology. Comparisons with previous results indicate that similar processes occur in the wild-type protein. The measured rates match the estimated Ca2+off rate, suggesting that Ca2+release may be gated by the conformational dynamics. Structural interpretation of estimated chemical shifts suggests a mechanism for ion release.

AB - Background: Calmodulin is a ubiquitous Ca2+-activated regulator of cellular processes in eukaryotes. The structures of the Ca2+-free (apo) and Ca2+-loaded states of calmodulin have revealed that Ca2+binding is associated with a transition in each of the two domains from a closed to an open conformation that is central to target recognition. However, little is known about the dynamics of this conformational switch. Results: The dynamics of the transition between closed and open conformations in the Ca2+-loaded state of the E140Q mutant of the calmodulin C-terminal domain were characterized under equilibrium conditions. The exchange time constants ($ex) measured for 42 residues range from 13 to 46 $s, with a mean of 21 \ 3 $s. The results suggest that $exvaries significantly between different groups of residues and that residues with similar values exhibit spatial proximity in the structures of apo and/or Ca2+-saturated wild-type calmodulin. Using data for one of these groups, we obtained an open population of po= 0.50 \ 0.17 and a closed \ open rate constant of ko= (2.7 \ 1.0) \ 104s-1. Conclusions: The conformational exchange dynamics appear to involve locally collective processes that depend on the structural topology. Comparisons with previous results indicate that similar processes occur in the wild-type protein. The measured rates match the estimated Ca2+off rate, suggesting that Ca2+release may be gated by the conformational dynamics. Structural interpretation of estimated chemical shifts suggests a mechanism for ion release.

KW - Conformational exchange

KW - Dynamics

KW - NMR

KW - Off-resonance rotating-frame N spin relaxation 15

U2 - 10.1016/S0969-2126(01)00575-5

DO - 10.1016/S0969-2126(01)00575-5

M3 - Journal article

VL - 9

JO - Word Structure

JF - Word Structure

SN - 1750-1245

IS - 3

ER -