Naslov
Helix Straightening as an Activation Mechanism in the Gelsolin Superfamily of Actin Regulatory Proteins

Autori
Wang, Hui ; Chumnarnsilpa, Sakesit ; Loonchanta, Anantasak ; Li, Qiang ; Kuan, Yang-Mei ; Robine, Sylvie ; Larsson, Mårten ; Mihalek, Ivana ; Burtnick, Leslie D. ; Robinson, Robert C.

Izvornik
Journal of Biological Chemistry (0021-9258) 284 (2009), 32; 21265-21269

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
galsolin ; cell motility ; molcular dynamics simulaton

Sažetak
Villin and gelsolin consist of six homologous domains of thegelsolin/cofilin fold (V1–V6 and G1–G6, respectively). Villindiffers from gelsolin in possessing at its C terminus an unrelatedseventh domain, the villin headpiece. Here, we present the crys-tal structure of villin domain V6 in an environment in whichintact villin would be inactive, in the absence of bound Ca2
orphosphorylation. The structure of V6 more closely resemblesthat of the activated form of G6, which contains one boundCa2
, rather than that of the calcium ion-free form of G6 withinintact inactive gelsolin. Strikingly apparent is that the long helixin V6 is straight, as found in the activated form of G6, as opposedto the kinked version in inactive gelsolin. Molecular dynamicscalculations suggest that the preferable conformation for thishelix in the isolated G6 domain is also straight in the absence ofCa2
and other gelsolin domains. However, the G6 helix bendsin intact calcium ion-free gelsolin to allow interaction with G2and G4. We suggest that a similar situation exists in villin.Within the intact protein, a bent V6 helix, when triggered byCa2
, straightens and helps push apart adjacent domains toexpose actin-binding sites within the protein. The sixth domainin this superfamily of proteins serves as a keystone that lockstogether a compact ensemble of domains in an inactive state.Perturbingthekeystoneinitiatesreorganizationofthestructureto reveal previously buried actin-binding sites

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Računarstvo, Biotehnologija, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA