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Computational prediction of O-linked glycosylation sites that preferentially map on intrinsically disordered regions of extracellular proteins.

Nishikawa I, Nakajima Y, Ito M, Fukuchi S, Homma K, Nishikawa K - Int J Mol Sci (2010)

Bottom Line: O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically.The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions.This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.

View Article: PubMed Central - PubMed

Affiliation: College of Information Science and Engineering, Ritsumeikan University/Noji-higashi 1-1-1, Kusatsu, Shiga 525-8577, Japan; E-Mail: nakajima.yukiko@gmail.com.

ABSTRACT
O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.

Show MeSH
(a) Existence ratios of Pro at each position for clustered positive, isolated positive, and negative Ser or Thr sites (indicated by red crosses, blue crosses, and pink triangles, respectively). Existence ratios of Val (b) and Ala (c) shown in a similar style.
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f3-ijms-11-04991: (a) Existence ratios of Pro at each position for clustered positive, isolated positive, and negative Ser or Thr sites (indicated by red crosses, blue crosses, and pink triangles, respectively). Existence ratios of Val (b) and Ala (c) shown in a similar style.

Mentions: The existence ratio or probability was calculated for 20 types of amino acids at a relative position from the glycosylation site for clustered and isolated glycosylations separately. As a typical example of the results, Figure 3(a) shows the existence ratio of proline (Pro) at each relative position within Ws = 31 around the clustered positive, isolated positive, and negative Ser and Thr residues. Pro has a high ratio at −1 and +3 relative to the O-glycosylation site [38]. In the figure, the high peak can be noted at −1 only for isolated glycosylation and at +3 for both types. The peak at −1 leads to the high prediction accuracy even at Ws = 3 for the isolated type shown in Figure 1.


Computational prediction of O-linked glycosylation sites that preferentially map on intrinsically disordered regions of extracellular proteins.

Nishikawa I, Nakajima Y, Ito M, Fukuchi S, Homma K, Nishikawa K - Int J Mol Sci (2010)

(a) Existence ratios of Pro at each position for clustered positive, isolated positive, and negative Ser or Thr sites (indicated by red crosses, blue crosses, and pink triangles, respectively). Existence ratios of Val (b) and Ala (c) shown in a similar style.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100847&req=5

f3-ijms-11-04991: (a) Existence ratios of Pro at each position for clustered positive, isolated positive, and negative Ser or Thr sites (indicated by red crosses, blue crosses, and pink triangles, respectively). Existence ratios of Val (b) and Ala (c) shown in a similar style.
Mentions: The existence ratio or probability was calculated for 20 types of amino acids at a relative position from the glycosylation site for clustered and isolated glycosylations separately. As a typical example of the results, Figure 3(a) shows the existence ratio of proline (Pro) at each relative position within Ws = 31 around the clustered positive, isolated positive, and negative Ser and Thr residues. Pro has a high ratio at −1 and +3 relative to the O-glycosylation site [38]. In the figure, the high peak can be noted at −1 only for isolated glycosylation and at +3 for both types. The peak at −1 leads to the high prediction accuracy even at Ws = 3 for the isolated type shown in Figure 1.

Bottom Line: O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically.The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions.This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.

View Article: PubMed Central - PubMed

Affiliation: College of Information Science and Engineering, Ritsumeikan University/Noji-higashi 1-1-1, Kusatsu, Shiga 525-8577, Japan; E-Mail: nakajima.yukiko@gmail.com.

ABSTRACT
O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.

Show MeSH