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Colloids Surf B Biointerfaces. 2014 Sep 1;121:307-18. doi: 10.1016/j.colsurfb.2014.05.028. Epub 2014 Jun 23.

Structural and dynamic investigation of bovine folate receptor alpha (FOLR1), and role of ultra-high temperature processing on conformational and thermodynamic characteristics of FOLR1-folate complex.

Author information

1
Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India; Laboratory of Molecular Biophysics, Institute for Protein Research, Osaka University, Osaka Prefecture, 5650871, Japan. Electronic address: bikash.bioinformatics@gmail.com.
2
Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India; Biotechnology Laboratory, Central Inland Fisheries Research Institute, Barrackpore, Kolkata, West Bengal, 700120, India.
3
Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India; Animal Genomics Laboratory, Animal Biotechnology Centre, National Dairy Research Institute, Karnal 132001, India.
4
Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar, 751001, India.
5
Immunology Frontier Research Centre, Osaka University, Osaka Prefecture, 5650871, Japan.
6
RIKEN Center for Life Science Technologies, Yokohama, 2300045, Japan.
7
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, 785013, Assam, India.

Abstract

The folate receptor alpha (FOLR1) present in milk has widely been studied to investigate the effects of pasteurization, ultra-high temperature (UHT) processing and fermentation on net folate concentration. However, the folate binding mechanism with FOLR1, and effect of temperature on FOLR1-folate complex is poorly explored till now in bovine milk which is a chief resource of folate. Despite of enormous importance of folic acid and the routine intake of bovine milk, folic acid deficiency diseases are common in human race. To understand the folate deficiency in milk after processing, in absence of experimental structure, 3D model of bovine FOLR1 (bvFOLR1) was built followed by 40ns molecular dynamics (MD) simulation. The folate and its derivatives binding sites in bvFOLR1 were anticipated by molecular docking using AutoDock 4.2. Essential MD studies suggested the presence of a longer signal peptide (22 residues) and a short propeptide (7 residues) at the C-terminus that may cleaved during post-translational modification. MD analysis of bvFOLR1-folate complex at 298, 323, 353, 373 and 408K followed by binding energy (BE) calculation showed maximum binding affinity at ∼353K. However, at 373K and UHT (408K), the folate BE is significantly decreased with substantial conformational alteration. Heating at UHT followed by cooling within 298-408K range demoed no structural reformation with temperature reduction, and the folate was displaced from the active site. This study presented the disintegration of folate from bvFOLR1 during high temperature processing and revealed a lower folate concentration in UHT milk and dairy products.

KEYWORDS:

Binding energy; Bovine; FOLR1; Folate; Molecular dynamics; Ultra-high temperature

PMID:
25023142
DOI:
10.1016/j.colsurfb.2014.05.028
[Indexed for MEDLINE]
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