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@ARTICLE{Dubovskii:478829,
author = {Dubovskii, Peter V. and Dubova, Kira M. and Bourenkov, Gleb
and Starkov, Vladislav G. and Konshina, Anastasia G. and
Efremov, Roman G. and Utkin, Yuri N. and Samygina, Valeriya
R.},
title = {{V}ariability in the {S}patial {S}tructure of the {C}entral
{L}oop in {C}obra {C}ytotoxins {R}evealed by {X}-ray
{A}nalysis and {M}olecular {M}odeling},
journal = {Toxins},
volume = {14},
number = {2},
issn = {2072-6651},
address = {Basel},
publisher = {MDPI},
reportid = {PUBDB-2022-02779},
pages = {149},
year = {2022},
abstract = {Cobra cytotoxins (CTs) belong to the three-fingered protein
family and possess membrane activity. Here, we studied
cytotoxin 13 from Naja naja cobra venom (CT13Nn). For the
first time, a spatial model of CT13Nn with both “water”
and “membrane” conformations of the central loop
(loop-2) were determined by X-ray crystallography. The
“water” conformation of the loop was frequently
observed. It was similar to the structure of loop-2 of
numerous CTs, determined by either NMR spectroscopy in
aqueous solution, or the X-ray method. The “membrane”
conformation is rare one and, to date has only been observed
by NMR for a single cytotoxin 1 from N. oxiana (CT1No) in
detergent micelle. Both CT13Nn and CT1No are S-type CTs.
Membrane-binding of these CTs probably involves an
additional step—the conformational transformation of the
loop-2. To confirm this suggestion, we conducted molecular
dynamics simulations of both CT1No and CT13Nn in the Highly
Mimetic Membrane Model of
palmitoiloleoylphosphatidylglycerol, starting with their
“water” NMR models. We found that the both toxins
transform their “water” conformation of loop-2 into the
“membrane” one during the insertion process. This
supports the hypothesis that the S-type CTs, unlike their
P-type counterparts, require conformational adaptation of
loop-2 during interaction with lipid membranes.},
cin = {EMBL-User / EMBL},
ddc = {610},
cid = {I:(DE-H253)EMBL-User-20120814 / I:(DE-H253)EMBL-20120731},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35202176},
UT = {WOS:000762016100001},
doi = {10.3390/toxins14020149},
url = {https://bib-pubdb1.desy.de/record/478829},
}