Single-molecule pair studies of the interactions of the alpha-GalNAc (Tn-antigen) form of porcine submaxillary mucin with soybean agglutinin.
Single-molecule pair studies of the interactions of the alpha-GalNAc (Tn-antigen) form of porcine submaxillary mucin with soybean agglutinin.
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猪颌下粘蛋白的 α-GalNAc（Tn 抗原）形式与大豆凝集素相互作用的单分子对研究。
DOI：
10.1002/bip.21213
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发表时间：
2009
期刊：
影响因子：
2.9
通讯作者：
Brewer,CurtisFred
中科院分区：
文献类型：
--
作者：
Sletmoen,Marit;Dam,TarunK;Gerken,ThomasA;Stokke,BjørnT;Brewer,CurtisFred
粘蛋白是一组高度糖基化的具有重要生物学意义的糖蛋白，参与多种生物学功能，包括调节免疫反应、炎症和粘附。粘蛋白也参与癌症和转移，经常表达诊断性癌症抗原。最近，一种含有GalNAcα1‐O‐Ser/Thr残基的改良猪上颌下粘蛋白（Tn‐PSM）被证明与大豆凝集素（SBA）结合，其亲和力比胰腺癌碳水化合物抗原GalNAcα1‐O‐Ser提高了约106倍。在这项研究中，动态力谱用于研究SBA和Tn - PSM的分子对。在与粘蛋白链长度一致的2.0 μm范围内，观察到许多表明解结合或再结合事件的力跳跃。随着力加载率的增加，解结合力从103 pN增加到402 pN。激活势垒在相互作用能量图中的位置为0.1 nm。在没有施加外力的情况下，SBA-TnPSM复合物的寿命在1.3-1.9 s之间。描述其他凝集素相互作用解离速率的动力学参数在3.3 × 10−3-2.5 × 10−3s范围内。SBA - TnPSM复合物的长寿命与凝集素分子沿着Tn - PSM的多肽链从α‐GalNAc残基“结合并跳跃”到α‐GalNAc残基的结合模型兼容，然后解离。这些发现对粘蛋白的分子识别特性具有重要意义。©2009 Wiley期刊公司生物工程学报（英文版），2009。本文最初作为可接受的预印本在网上发表。“在线发布”日期对应于预印本。您可以通过发送电子邮件至biopolymers@wiley.com向Biopolymers编辑部索取预印本
Mucins form a group of heavilyO‐glycosylated biologically important glycoproteins that are involved in a variety of biological functions, including modulating immune response, inflammation, and adhesion. Mucins are also involved in cancer and metastasis and often express diagnostic cancer antigens. Recently, a modified porcine submaxillary mucin (Tn‐PSM) containing GalNAcα1‐O‐Ser/Thr residues was shown to bind to soybean agglutinin (SBA) with ∼106‐fold enhanced affinity relative to GalNAcα1‐O‐Ser, the pancarcinoma carbohydrate antigen. In this study, dynamic force spectroscopy is used to investigate molecular pairs of SBA and Tn‐PSM. A number of force jumps that demonstrate unbinding or rebinding events were observed up to a distance equal to 2.0 μm, consistent with the length of the mucin chain. The unbinding force increased from 103 to 402 pN with increasing force loading rate. The position of the activation barrier in the energy landscape of the interaction was 0.1 nm. The lifetime of the SBA–TnPSM complex in the absence of applied force was determined to be in the range 1.3–1.9 s. Kinetic parameters describing the rate of dissociation of other sugar lectin interactions are in the range 3.3 × 10−3–2.5 × 10−3s. The long lifetime of the SBA‐TnPSM complex is compatible with a binding model in which lectin molecules “bind and jump” from α‐GalNAc residue to α‐GalNAc residue along the polypeptide chain of Tn‐PSM before dissociating. These findings have important implications for the molecular recognition properties of mucins. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 719–728, 2009.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com