日前，美國《國家科學(xué)院院刊》（PNAS）在線發(fā)表了國家納米科學(xué)中心科研人員的淀粉樣蛋白結(jié)構(gòu)解析的新進(jìn)展。研究人員利用掃描隧道顯微技術(shù)（STM）對(duì)2型糖尿病相關(guān)的淀粉樣蛋白——胰淀素的組裝和聚集結(jié)構(gòu)進(jìn)行研究,，確定了淀粉樣蛋白組裝和聚集的核心片段及折疊位點(diǎn),，并討論了突變引起的聚集趨勢(shì)的變化與核心片段之間的關(guān)聯(lián),。對(duì)理解淀粉樣蛋白的核心片段與其致病性之間的關(guān)系有重要意義,。
理解淀粉樣蛋白的折疊結(jié)構(gòu)和聚集行為是檢測(cè)和治療淀粉樣病變的關(guān)鍵所在,。但是由于淀粉樣蛋白不易結(jié)晶，而且溶解性差,，使得結(jié)構(gòu)解析非常困難,。近幾年來，國家納米科學(xué)中心科研人員發(fā)展了一種利用小分子調(diào)節(jié)劑有效調(diào)控淀粉樣蛋白聚集的新方法,，探索在分子水平上開展對(duì)淀粉樣多肽的結(jié)構(gòu)的解析研究,，進(jìn)一步發(fā)現(xiàn)通過調(diào)控其組裝結(jié)構(gòu)和聚集過程可以有效地降低淀粉樣多肽的細(xì)胞毒性。參與此研究的骨干成員毛曉波,、王晨軒等還利用掃描隧道顯微方法研究了淀粉樣多肽與標(biāo)記分子的結(jié)合模式,。這些工作提出了一種新穎的淀粉樣多肽結(jié)構(gòu)解析方法，而且從分子水平上揭示了多肽與分子調(diào)節(jié)劑相互作用的機(jī)理,，為與淀粉樣蛋白聚集有關(guān)的疾病預(yù)防,、藥物設(shè)計(jì)和治療提供了新思路。（生物谷Bioon.com）
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doi:10.1073/pnas.1102971108
PMC:
PMID:
Beta structure motifs of islet amyloid polypeptides identified through surface-mediated assemblies
Mao, Xiao-Bo; Wang, Chen-Xuan; Wu, Xing-Kui; Ma, Xiao-Jing; Liu, Lei; Zhang, Lan; Niu, Lin; Guo, Yuan-Yuan; Li, Deng-Hua; Yang, Yan-Lian; Wang, Chen
We report here the identification of the key sites for the beta structure motifs of the islet amyloid polypeptide (IAPP) analogs by using scanning tunneling microscopy (STM). Duplex folding structures in human IAPP8–37 (hIAPP8–37) assembly were observed featuring a hairpin structure. The multiplicity in rIAPP assembly structures indicates the polydispersity of the rat IAPP8–37 (rIAPP8–37) beta-like motifs. The bimodal length distribution of beta structure motifs for rIAPP8–37 R18H indicates the multiple beta segments linked by turns. The IAPP8–37 analogs share common structure motifs of IAPP8–17 and IAPP26–37 with the most probable key sites at positions around Ser19/Ser20 and Gly24. These observations reveal the similar amyloid formation tendency in the C and N terminus segments because of the sequence similarity, while the differences in specific amino acids at each key site manifest the effect of sequence variations. The results could be beneficial for studying structural polymorphism of amyloidal peptides with multiple beta structure motifs.
