Interactions between anti-ErbB2 antibody A21 and the ErbB2 extracellular domain provide a basis for improving A21 affinity

Chang Liang; Zhou Changhai; Xu Man; Liu Jing

Chinese︱Feedback︱Save this page

• Elaborating Academic Views 　　　　 • Exchanging Innovative Ideas
• Protecting Intellectual Properties 　　• Fast Sharing Science Papers

Sponsored by the Center for Science and Technology Development of the Ministry of Education
Supervised by Ministry of Education of the People's Republic of China

Home > Papers

Interactions between anti-ErbB2 antibody A21 and the ErbB2 extracellular domain provide a basis for improving A21 affinity

Chang Liang ,Zhou Changhai ,Xu Man,Liu Jing * #

School of Life Sciences,University of Science and Technology of China

*Correspondence author

#Submitted by

Subject:

Funding: 国家自然科学基金,教育部博士点基金,国家863重点项,科技重大专项重大新药创制（No.30570362,20060358021,2006AA02A245,2009zx09102-223）

Opened online: 1 February 2010

Accepted by: none

Citation: Chang Liang ,Zhou Changhai ,Xu Man.Interactions between anti-ErbB2 antibody A21 and the ErbB2 extracellular domain provide a basis for improving A21 affinity [OL]. [ 1 February 2010] http://en.paper.edu.cn/en_releasepaper/content/39758

Anti-ErbB2 antibodies are well researched for the therapy of ErbB2-overexpressing tumors. The therapeutic potential and efficacy of these antibodies are closely related to their affinities to ErbB2. Previously we reported that an anti-ErbB2 antibody A21 targeting a conformational epitope comprising several loops in ErbB2 extracellular subdomain I and II could inhibit the proliferation of ErbB2-overexpressing cancer cells in vitro and in vivo. Here we found that another structureless and non-conserved loop in subdomain I of ErbB2 extracellular domain (ECD) was important for binding to A21, and then the antigen-contact sites on A21 were determined by site-directed mutation. The loop was constructed by molecular modeling, and a new model of A21-ErbB2 complex was generated by docking using the crystal structure of the scfv A21 and the model of ErbB2 ECD with the loop built. Based on the complex model, computational design for A21 affinity improvement was performed to enhance its affinity to ErbB2. Two mutants with about 1.7-fold improvement in affinity were obtained. Our study provided a rational molecular basis for affinity improvement and mechanism investigation of A21.

Keywords:Epitope loop;Internalizing antibody;Docking;Inhibitory mechanism

For this paper

● PDF (0B)
● Revision 0 　　
● Print this paper
● Recommend this paper to a friend
● Add to my favorite list

Saved Papers

Please enter a name for this paper to be shown in your personalized Saved Papers list

Tags

Add yours

Related Papers

Statistics

PDF Downloaded	345
Bookmarked	0
Recommend	5
Comments	Array

Submit your papers

Alert Name:
Alerting to:
Authentication email will be sent to your email address in 24 hours
Frequency:
Email Message Format:	Plain text Graphical(HTML)

Complete the form below and we will recommend the selected titles to your friends on your behalf. * Indicates a required field.
Your name*:
Your email address*:
Recipient's name*:
Recipient's email address*:
(multiple recipient's names and email addresses should be separated with semicolons)
Your comments:	I thought you would find the page(s) useful.

Your name:
Your email address:
Recipient's name:
Recipient's email address:
(multiple recipient's names and email addresses should be separated with semicolons)
Your comments:	I thought you would find this page useful.

Disclaimer: This message was sent to your friend using the "Send it to a friend" facility on the Sciencepaper Online’ WWW site, http://www.paper.edu.cn/en. The Sciencepaper Online is not responsible for the content of this email, and anything said in this email does not necessarily reflect the Sciencepaper Online's views.

	Check out RSS, or use RSS reader to subscribe this item

Saved Papers