FIGURE 3. The membrane-embedded active site of rhomboid protease
a, b, Mutagenesis studies on Drosophila Rhomboid-1 and other rhomboid proteases mapped onto GlpG (viewing angle as in Fig. 2a, b). The GLSG (Gly 199, Ser 201) motif and His 254 are shown in red; His 150 and Asn 154 in orange; Trp 136 and Arg 137 in yellow. Alanine substitution of an arginine in Rhomboid-1 that corresponds to Lys 173 of GlpG (green) also affects activity12: this residue may have a structural function. Alanine substitutions of those residues shown in white do not affect activity12. c, The internal hydrophilic cavity and its front opening. For clarity, the lateral gate (L1) and the cap (L5) have been omitted. The asterisk marks the location of His 254 towards the back of the cavity. The molecular surface is generated by GRASP49. d, A detailed view of the active site and the hydrogen bond network surrounding the catalytic Ser 201 and His 254 (pink). WAT, water molecule (isolated red dots). Only parts of L1, S2, L3, S4, S5 and S6 are shown for clarity. e, Bound water molecules (yellow spheres) within the active site in relation to the conserved GLSG motif and His 254 (red). The boundaries for the hydrophobic region of the membrane are marked by horizontal lines.
生物谷報道：Rhomboid蛋白酶是一種專在膜內(nèi)發(fā)揮作用的蛋白家族,，該家族的蛋白可分解其他蛋白的跨膜結(jié)構(gòu)域：很多信號蛋白經(jīng)過膜內(nèi)蛋白水解而處于活性狀態(tài),，而其他一些信號蛋白則轉(zhuǎn)化成溶解性較差的,、淀粉質(zhì)的多肽片段．
近期,，美國耶魯大學(xué)醫(yī)學(xué)院的學(xué)者,，成功確定了Rhomboid蛋白的一個家族成員――存在于大腸桿菌中的GlpG――的晶體結(jié)構(gòu)，該結(jié)構(gòu)顯示了它是怎樣利用來自膜外的水分子來解離嵌入在膜中的蛋白基質(zhì)的,。這一研究結(jié)果發(fā)表于最新一期的《Nature》雜志上,。此外，催化類似反應(yīng)的其他Rhomboid家族蛋白也可能有這一機(jī)制,。其中的一個,，即Presenilin，所發(fā)生的突變與家族性阿爾茨海默氏癥有關(guān),。
原文出處:
Nature Volume 444 Number 7116 pp123-242
Crystal structure of a rhomboid family intramembrane protease p179
Yongcheng Wang, Yingjiu Zhang and Ya Ha
Abstract | Full Text | PDF (872K) | Supplementary information
相關(guān)文獻(xiàn):
Nature Volume 444 Number 7116 pp123-242
Structural biology: Enzyme theory holds water p153
Intramembrane proteases have attracted much attention because of their biological and medical value. The first crystal structure of one of these enzymes begins to solve the mystery of how they work.
Matthew Freeman
Full Text | PDF (348K)
