原创力文档animal ca2+ release-activated ca2+ (crac) channels appear to be homologous to and derived from the ubiquitous cation diffusion facilitators动物ca2 + release-activated ca2 +(坚固)通道似乎同源和来自无处不在的阳离子扩散助理员.pdfVIP
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animalca2release-activatedca2(crac)channelsappeartobehomologoustoandderivedfromtheubiquitouscationdiffusionfacilitators动物ca2release-activatedca2(坚固)通道似乎同源和来自无处不在的阳离子扩散助理员
Matias et al. BMC Research Notes 2010, 3:158
/1756-0500/3/158
S HO RT REPORT Open Access
Short Report 2+ 2+
Animal Ca release-activated Ca (CRAC)
channels appear to be homologous to and derived
from the ubiquitous cation diffusion facilitators
Madeleine G Matias, Kenny M Gomolplitinant, Dorjee G Tamang and Milton H Saier Jr*
Abstract
Background: Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC)
channels, promoting an immune response to pathogens. Defects in a CRAC (Orai) channel in humans gives rise to the
hereditary Severe Combined Immune Deficiency (SCID) syndrome. We here report results that define the evolutionary
relationship of the CRAC channel proteins of animals, and the ubiquitous Cation Diffusion Facilitator (CDF) carrier
proteins.
Findings: CDF antiporters derived from a primordial 2 transmembrane spanner (TMS) hairpin structure by intragenic
triplication to yield 6 TMS proteins. Four programs (IC/GAP, GGSEARCH, HMMER and SAM) were evaluated for
identifying sequence similarity and establishing homology using statistical means. Overall, the order of sensitivity
(similarity detection) was IC/GAP = GGSEARCH HMMER SAM, but the use of all four programs was superior to the
use of any two or three of them. Members of the CDF family appeared to be homologous to members of the 4 TMS
Orai channel proteins.
Conclusions: CRAC channels derived from CDF carriers by loss of the first two TMSs of the latter. Based on statistical
analyses with multiple programs, TMSs 3-6 in CDF carriers are homologous to TMSs 1-4 in CRAC channels, and the
former was the precursor of the latter. This is an unusual example of how a function
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