Intrinsic property of phenylalanine to trigger protein aggregation and hemolysis has a direct relevance to phenylketonuria

被引:60
作者
Anand, Bibin G. [2 ]
Dubey, Kriti [2 ]
Shekhawat, Dolat S. [2 ]
Kar, Karunakar [1 ]
机构
[1] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India
[2] Indian Inst Technol Jodhpur, Dept Biosci & Bioengn, Jodhpur 340012, Rajasthan, India
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
GLOBULAR-PROTEINS; AMYLOID FORMATION; FIBRILS; OLIGOMERS; CONTRAST;
D O I
10.1038/s41598-017-10911-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Excess accumulation of phenylalanine is the characteristic of untreated Phenylketonuria (PKU), a well-known genetic abnormality, which triggers several neurological, physical and developmental severities. However, the fundamental mechanism behind the origin of such diverse health problems, particularly the issue of how they are related to the build-up of phenylalanine molecules in the body, is largely unknown. Here, we show cross-seeding ability of phenylalanine fibrils that can effectively initiate an aggregation process in proteins under physiological conditions, converting native protein structures to beta-sheet assembly. The resultant fibrils were found to cause severe hemolysis, yielding a plethora of deformed erythrocytes that is highly relevant to phenylketonuria. Unique arrangement of zwitterionic phenylalanine molecules in their amyloid-like higher order entities is predicted to promote both hydrophobic and electrostatic interaction, sufficient enough to trap proteins and to preferentially interact with the membrane components of RBCs. Since the prevalence of hemolysis and amyloid related psychoneurological severities are mostly observed in PKU patients, we propose that the inherent property of phenylalanine fibrils to trigger hemolysis and to induce protein aggregation may have direct relevance to the disease mechanism of PKU.
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页数:9
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共 41 条
[11]   Amyloid fibrils from muscle myoglobin -: Even an ordinary globular protein can assume a rogue guise if conditions are right. [J].
Fändrich, M ;
Fletcher, MA ;
Dobson, CM .
NATURE, 2001, 410 (6825) :165-166
[12]   Protein aggregation: folding aggregates, inclusion bodies and amyloid [J].
Fink, AL .
FOLDING & DESIGN, 1998, 3 (01) :R9-R23
[13]   Albumin: Pathophysiologic Basis of Its Role in the Treatment of Cirrhosis and Its Complications [J].
Garcia-Martinez, Rita ;
Caraceni, Paolo ;
Bernardi, Mauro ;
Gines, Pere ;
Arroyo, Vicente ;
Jalan, Rajiv .
HEPATOLOGY, 2013, 58 (05) :1836-1846
[14]   Self-Assembly of Phenylalanine-Based Molecules [J].
German, Helen W. ;
Uyaver, Sahin ;
Hansmann, Ulrich H. E. .
JOURNAL OF PHYSICAL CHEMISTRY A, 2015, 119 (09) :1609-1615
[15]   Expanding the Nanoarchitectural Diversity Through Aromatic Di- and Tri-Peptide Coassembly: Nanostructures and Molecular Mechanisms [J].
Guo, Cong ;
Amon, Zohar A. ;
Qi, Ruxi ;
Zhang, Qingwen ;
Adler-Abramovich, Lihi ;
Gazit, Ehud ;
Wei, Guanghong .
ACS NANO, 2016, 10 (09) :8316-8324
[16]  
Hall DM, 2016, NAT MATER, V15, P727, DOI [10.1038/NMAT4598, 10.1038/nmat4598]
[17]   MALNUTRITION WITH EARLY TREATMENT OF PHENYLKETONURIA [J].
HANLEY, WB ;
LINSAO, L ;
DAVIDSON, W ;
MOES, CAF .
PEDIATRIC RESEARCH, 1970, 4 (04) :318-+
[18]   Red cell perturbations by amyloid β-protein [J].
Jayakumar, R ;
Kusiak, JW ;
Chrest, FJ ;
Demehin, AA ;
Murali, J ;
Wersto, RP ;
Nagababu, E ;
Ravi, L ;
Rifkind, JM .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2003, 1622 (01) :20-28
[19]   D-Polyglutamine Amyloid Recruits L-Polyglutamine Monomers and Kills Cells [J].
Kar, Karunakar ;
Arduini, Irene ;
Drombosky, Kenneth W. ;
van der Wel, Patrick C. A. ;
Wetzel, Ronald .
JOURNAL OF MOLECULAR BIOLOGY, 2014, 426 (04) :816-829
[20]   Identification of disulfide cross-linked tau dimer responsible for tau propagation [J].
Kim, Dohee ;
Lim, Sungsu ;
Haque, Md. Mamunul ;
Ryoo, Nayeon ;
Hong, Hyun Seok ;
Rhim, Hyewhon ;
Lee, Dong-Eun ;
Chang, Young-Tae ;
Lee, Jun-Seok ;
Cheong, Eunji ;
Kim, Dong Jin ;
Kim, Yun Kyung .
SCIENTIFIC REPORTS, 2015, 5