Computer simulation study of amyloid fibril formation by palindromic sequences in prion peptides.
Computer simulation study of amyloid fibril formation by palindromic sequences in prion peptides.
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DOI：
10.1002/prot.23034
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发表时间：
2011-07
影响因子：
2.9
通讯作者：
Hall, Carol K.
中科院分区：
文献类型：
--
作者：
Wagoner, Victoria A.;Cheon, Mookyung;Chang, Iksoo;Hall, Carol K.
我们模拟了含有叙利亚仓鼠朊蛋白SHaPrP 113-120 （AGAAAAGA）和小鼠朊蛋白mprp 111-120 （VAGAAAAGAV）回文肽的大系统的聚集，以及8种序列变异：GAAAAAAG， （AG）4, A8， GAAAGAAA, A10, V10， GAVAAAAVAG和VAVAAAAVAV。前两种肽被认为是将亲本朊蛋白在淀粉样蛋白结构中结合在一起的尼龙扣，它们自己可以形成原纤维。沿成纤维途径的动力学事件影响发生的结构类型，序列的变化影响聚集动力学和纤维结构。使用PRIME20力场对含有48个肽的系统进行了不连续分子动力学模拟，从随机线圈结构开始。根据序列的不同，纤维状结构会在一定温度范围内自发形成，低于该温度会形成无定形聚集体，高于该温度则不会形成聚集体。AGAAAAGA形成组织良好的纤维状结构，而VAGAAAAGAV形成组织较差的结构，部分为纤维状，部分为无定形。纤维结构的有序程度部分源于导致其形成的动力学事件的类型，在模拟的早期，AGAAAAGA形成的无定形结构比VAGAAAAGAV少。形成原纤维的能力随着链长度和疏水残基拉伸长度的增加而增加。然而，随着序列疏水性的增加，形成有序结构的能力下降。因此，较长的疏水序列形成轻微无序的聚集体，部分为纤维状，部分为无定形。序列的细微变化导致纤维结构略有不同。
We simulate the aggregation of large systems containing palindromic peptides from the Syrian hamster prion protein SHaPrP 113–120 (AGAAAAGA) and the mouse prion protein MoPrP 111–120 (VAGAAAAGAV) and eight sequence variations: GAAAAAAG, (AG)4, A8, GAAAGAAA, A10, V10, GAVAAAAVAG, and VAVAAAAVAV The first two peptides are thought to act as the Velcro that holds the parent prion proteins together in amyloid structures and can form fibrils themselves. Kinetic events along the fibrillization pathway influence the types of structures that occur and variations in the sequence affect aggregation kinetics and fibrillar structure. Discontinuous molecular dynamics simulations using the PRIME20 force field are performed on systems containing 48 peptides starting from a random coil configuration. Depending on the sequence, fibrillar structures form spontaneously over a range of temperatures, below which amorphous aggregates form and above which no aggregation occurs. AGAAAAGA forms well organized fibrillar structures whereas VAGAAAAGAV forms less well organized structures that are partially fibrillar and partially amorphous. The degree of order in the fibrillar structure stems in part from the types of kinetic events leading up to its formation, with AGAAAAGA forming less amorphous structures early in the simulation than VAGAAAAGAV. The ability to form fibrils increases as the chain length and the length of the stretch of hydrophobic residues increase. However as the hydrophobicity of the sequence increases, the ability to form well-ordered structures decreases. Thus, longer hydrophobic sequences form slightly disordered aggregates that are partially fibrillar and partially amorphous. Subtle changes in sequence result in slightly different fibril structures.
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影响因子：
2.9
作者：
Cheon, Mookyung;Chang, Iksoo;Hall, Carol K.
通讯作者：
Hall, Carol K.
DOI：
10.1073/pnas.2433563100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Kuwata, K;Matumoto, T;Roder, H
通讯作者：
Roder, H
影响因子：
8
作者：
Ma, BY;Nussinov, R
通讯作者：
Nussinov, R
影响因子：
5.6
作者：
Lee, Shin-Wen;Mou, Yun;Chan, Jerry C. C.
通讯作者：
Chan, Jerry C. C.
DOI：
10.1073/pnas.230315097
发表时间：
2000-11-21
影响因子：
11.1
作者：
Antzutkin, ON;Balbach, JJ;Tycko, R
通讯作者：
Tycko, R