4.7 Article

Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins

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SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -

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NATURE RESEARCH
DOI: 10.1038/s41598-020-61427-y

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资金

  1. DBT [0525]
  2. Wellcome Trust DBT India Alliance Fellowship [WELT0041]
  3. IISc
  4. DST-FIST [SR/FST/LS11-036/2014(C)]
  5. UGC-SAP [F.4.13/2018/DRS-III (SAP-II)]
  6. DBT-IISc Partnership Program Phase-II [BT/PR27952-INF/22/212/2018]
  7. Indian Council of Medical Research (Ministry of Health AMP
  8. Family Welfare, Government of India)
  9. Department of Biotechnology (Ministry of Science and Technology, Government of India)

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Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions. However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order. When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans. We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures. When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and beta structures. N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions. Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.

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