Effect of Single Amino Acid Substitutions by Asn and Gln on Aggregation Properties of Bence-Jones Protein BIF.
Int J Mol Sci
; 20(20)2019 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-31635169
ABSTRACT
The nature of renal amyloidosis involving Bence-Jones proteins in multiple myeloma is still unclear. The development of amyloidosis in neurodegenerative diseases is often associated with a high content of asparagine and glutamine residues in proteins forming amyloid deposits. To estimate the influence of Asn and Gln residues on the aggregation of Bence-Jones protein BIF, we obtained recombinant BIF and its mutants with the substitution of Tyr187âAsn (Y187N) in α-helix of CL domain, Lys170âAsn (K170N) and Ser157âGln (S157Q) in CL domain loops, Arg109âAsn in VL-CL linker (R109N) and Asp29âGln in VL domain loop (D29Q). The morphology of protein aggregates was studied at pH corresponding to the conditions in bloodstream (pH 7.2), distal (pH 6.5) and proximal renal tubules (pH 4.5) by atomic force microscopy (AFM) and small-angle X-ray scattering (SAXS). The Lys170âAsn replacement almost completely inhibits amyloidogenic activity. The Y187N forms fibril-like aggregates at all pH values. The Arg109âAsn replacement resulted in formation of fibril-like structures at pH 7.2 and 6.5 while the substitutions by Gln provoked formation of those structures only at pH 7.2. Therefore, the amyloidogenic properties are highly dependent on the location of Asn or Gln.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Asparagina
/
Proteína de Bence Jones
/
Proteínas Mutantes
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Agregado de Proteínas
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Glutamina
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2019
Tipo del documento:
Article
País de afiliación:
Rusia