Analysis of Protein Determinants Required for the Polysialylation of the Neural Cell Adhesion Molecule.

More About This Textbook


Polysialic acid is an anti-adhesive carbohydrate polymer that is expressed in a developmentally- regulated manner. In mammals, the main carrier of polysialic acid is the neural cell adhesion molecule, NCAM. Polysialylated NCAM has important functions in nervous system development, synaptic plasticity, and neuronal generation. Moreover, deregulated polysialic acid expression is associated with cancer metastasis and with the development of neuropsychiatric disorders.;Polysialylation is catalyzed by the polysialyltransferase enzymes, and is a protein-specific glycosylation event. The FN1 domain of NCAM is critical for the polysialylation of N-glycans located on the adjacent Ig5 domain. Our laboratory proposed that polysialyltransferases bind to the NCAM FN1 domain and in this way are positioned to polysialylate Ig5 N-glycans. Furthermore, the structure of the FN1 domain revealed the presence of a novel surface acidic patch and alpha-helix with roles in NCAM polysialylation.;In this study, the protein-specific polysialylation of NCAM was further investigated. We solved the crystal structure of the NCAM Ig5-FN1 tandem. The sites of polysialylation on Ig5 were found to be on the opposite face as the FN1 acidic patch and alpha-helix. However, the polysialylation of engineered N-glycans on the Ig5 domain revealed some flexibility in the polysialylation process. Furthermore, this analysis revealed that the polysialyltransferases must engage the Ig5 domain to prevent a redirection of polysialylation to O-glycans.;An alignment of the FN1 sequences of NCAM and the unpolysialylated protein, olfactory cell adhesion molecule (OCAM), revealed two unconserved sequences within NCAM FN1, Pro510-Tyr511-Ser512 (PYS), and Gln516-Val517-Gln 518 (QVQ). We found that the acidic patch and PYS are required for O-glycan polysialylation, while QVQ has a positioning role similar to the alpha-helix. Analysis of chimeric proteins revealed that OCAM FN1 allows partial polysialylation of NCAM Ig5 N-glycans, while the Ig5 domain of OCAM does not permit polysialylation.;Finally, a conserved polybasic region within the polysialyltransferases was identified. Specific residues within this sequence are required for NCAM polysialylation, but not enzyme activity, suggesting they may be required for the initial interaction with NCAM. We propose that altering this interaction would be an attractive method of regulating polysialic acid expression in disease states.
Read More Show Less

Product Details

  • BN ID: 2940043602176
  • Publisher: ProQuest LLC
  • Sold by: Barnes & Noble
  • Format: eTextbook
  • Pages: 190
  • File size: 9 MB

Customer Reviews

Be the first to write a review
( 0 )
Rating Distribution

5 Star


4 Star


3 Star


2 Star


1 Star


Your Rating:

Your Name: Create a Pen Name or

Barnes & Review Rules

Our reader reviews allow you to share your comments on titles you liked, or didn't, with others. By submitting an online review, you are representing to Barnes & that all information contained in your review is original and accurate in all respects, and that the submission of such content by you and the posting of such content by Barnes & does not and will not violate the rights of any third party. Please follow the rules below to help ensure that your review can be posted.

Reviews by Our Customers Under the Age of 13

We highly value and respect everyone's opinion concerning the titles we offer. However, we cannot allow persons under the age of 13 to have accounts at or to post customer reviews. Please see our Terms of Use for more details.

What to exclude from your review:

Please do not write about reviews, commentary, or information posted on the product page. If you see any errors in the information on the product page, please send us an email.

Reviews should not contain any of the following:

  • - HTML tags, profanity, obscenities, vulgarities, or comments that defame anyone
  • - Time-sensitive information such as tour dates, signings, lectures, etc.
  • - Single-word reviews. Other people will read your review to discover why you liked or didn't like the title. Be descriptive.
  • - Comments focusing on the author or that may ruin the ending for others
  • - Phone numbers, addresses, URLs
  • - Pricing and availability information or alternative ordering information
  • - Advertisements or commercial solicitation


  • - By submitting a review, you grant to Barnes & and its sublicensees the royalty-free, perpetual, irrevocable right and license to use the review in accordance with the Barnes & Terms of Use.
  • - Barnes & reserves the right not to post any review -- particularly those that do not follow the terms and conditions of these Rules. Barnes & also reserves the right to remove any review at any time without notice.
  • - See Terms of Use for other conditions and disclaimers.
Search for Products You'd Like to Recommend

Recommend other products that relate to your review. Just search for them below and share!

Create a Pen Name

Your Pen Name is your unique identity on It will appear on the reviews you write and other website activities. Your Pen Name cannot be edited, changed or deleted once submitted.

Your Pen Name can be any combination of alphanumeric characters (plus - and _), and must be at least two characters long.

Continue Anonymously

    If you find inappropriate content, please report it to Barnes & Noble
    Why is this product inappropriate?
    Comments (optional)