Probing transient non-native states in amyloid beta fiber elongation by NMR

被引:46
作者
Brender, Jeffrey R. [1 ,2 ]
Ghosh, Anirban [3 ]
Kotler, Samuel A. [2 ]
Krishnamoorthy, Janarthanan [1 ,2 ,4 ]
Bera, Swapna [3 ]
Morris, Vanessa [5 ]
Sil, Timir Baran [6 ]
Garai, Kanchan [6 ]
Reif, Bernd [5 ]
Bhunia, Anirban [1 ,2 ,3 ]
Ramamoorthy, Ayyalusamy [1 ,2 ,7 ]
机构
[1] Univ Michigan, Biophys, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[3] Bose Inst, Dept Biophys, Kolkata 700054, India
[4] VClinbio Labs Pvt Ltd, Sri Ramchandra Med Ctr, Chennai 600116, Tamil Nadu, India
[5] Tech Univ Munich, Dept Chem, Munich, Germany
[6] TIFR Ctr Interdisciplinary Sci, Hyderabad 500107, Telangana, India
[7] Tech Univ Munich, Inst Adv Studies, Munich, Germany
关键词
SECONDARY NUCLEATION; AGGREGATION; PROTOFIBRILS; DYNAMICS; RESOLUTION; MECHANISM; MONOMER; REVEALS;
D O I
10.1039/c9cc01067j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Using NMR to probe transient binding of A(1-40) monomers to fibers, we find partially bound conformations with the highest degree of interaction near F19-K28 and a lesser degree of interaction near the C-terminus (L34-G37). This represents a shift away from the KLVFFA recognition sequence (residues 16-21) currently used for inhibitor design.
引用
收藏
页码:4483 / 4486
页数:4
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