Calmodulin binds a highly extended HIV-1 MA protein that refolds upon its release.

Abstract:

:Calmodulin (CaM) expression is upregulated upon HIV-1 infection and interacts with proteins involved in viral processing, including the multifunctional HIV-1 MA protein. We present here the results of studies utilizing small-angle neutron scattering with contrast variation that, when considered in the light of earlier fluorescence and NMR data, show CaM binds MA in an extended open-clamp conformation via interactions with two tryptophans that are widely spaced in sequence and space. The interaction requires a disruption of the MA tertiary fold such that MA becomes highly extended in a long snakelike conformation. The CaM-MA interface is extensive, covering ~70% of the length of the MA such that regions known to be important in MA interactions with critical binding partners would be impacted. The CaM conformation is semiextended and as such is distinct from the classical CaM-collapse about short α-helical targets. NMR data show that upon dissociation of the CaM-MA complex, either by the removal of Ca(2+) or increasing ionic strength, MA reforms its native tertiary contacts. Thus, we observe a high level of structural plasticity in MA that may facilitate regulation of its activities via intracellular Ca(2+)-signaling during viral processing.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Taylor JE,Chow JYH,Jeffries CM,Kwan AH,Duff AP,Hamilton WA,Trewhella J

doi

10.1016/j.bpj.2012.06.042

subject

Has Abstract

pub_date

2012-08-08 00:00:00

pages

541-549

issue

3

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(12)00731-X

journal_volume

103

pub_type

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