کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5913763 | 1162701 | 2015 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85
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کلمات کلیدی
IPTGGAMCD44HSQCDmaxPDBscFvp(r)CDRFBSSAXSPBSMonoclonal antibody - آنتی بادی مونوکلونالisopropyl β-D-1-thiogalactopyranoside - ایزوپروپیل β-D-1-thiogalactopyranosideScattering vector - بردار پراکندهTev - به توNMR - تشدید مغناطیسی هستهای Surface plasmon resonance - تشدید پلاسمون سطحیSPR - تشدید پلاسمون سطحیMolecular mass - توده مولکولیfetal bovine serum - سرم جنین گاوRadius of gyration - شعاع نفوذgoat anti-mouse - ضد موش بزPhosphate buffered saline - فسفات بافر شورsingle-chain variable fragment - قطعه متغیر تک زنجیره ایOrdered - مرتب شدهcomplementarity determining region - منطقه تعریف مکملEpitope mapping - نقشه برداری اپیتوپwild type - نوع وحشیTobacco etch virus - ویروس تنباکو اچSmall-angle X-ray scattering - پراکندگی اشعه ایکس با زاویه کوچکForward scattering - پراکندگی به جلوProtein Data Bank - پروتئین بانک اطلاعاتیheteronuclear single quantum coherence - یکپارچگی کوانتومی تک هسته ای
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85 Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85](/preview/png/5913763.png)
چکیده انگلیسی
The hyaluronate receptor CD44 plays role in cell adhesion and migration and is involved in tumor metastasis. The extracellular domain of CD44 comprises the hyaluronate-binding domain (HABD) and the membrane-proximal stem region; the short intracellular portion interacts with adaptor proteins and triggers signaling pathways. Binding of hyaluronate to CD44 HABD induces an allosteric conformational change, which results in CD44 shedding. A poorly characterized epitope in human CD44 HABD is recognized by the murine monoclonal antibody MEM-85, which cross-blocks hyaluronate binding to CD44 and also induces CD44 shedding. MEM-85 is of therapeutic interest, as it inhibits growth of lung cancer cells in murine models. In this work, we employed a combination of biophysical methods to determine the MEM-85 binding epitope in CD44 HABD and to provide detailed insight into the mechanism of MEM-85 action. In particular, we constructed a single-chain variable fragment (scFv) of MEM-85 as a tool for detailed characterization of the CD44 HABD-antibody complex and identified residues within CD44 HABD involved in the interaction with scFv MEM-85 by NMR spectroscopy and mutational analysis. In addition, we built a rigid body model of the CD44 HABD-scFv MEM-85 complex using a low-resolution structure obtained by small-angle X-ray scattering. The MEM-85 epitope is situated in the C-terminal part of CD44 HABD, rather than the hyaluronate-binding groove, and the binding of MEM-85 induces a structural reorganization similar to that induced by hyaluronate. Therefore, the mechanism of MEM-85 cross-blocking of hyaluronate binding is likely of an allosteric, relay-like nature.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 191, Issue 2, August 2015, Pages 214-223
Journal: Journal of Structural Biology - Volume 191, Issue 2, August 2015, Pages 214-223
نویسندگان
Jana Å kerlová, Vlastimil Král, Michael Kachala, Milan Fábry, Ladislav Bumba, Dmitri I. Svergun, ZdenÄk ToÅ¡ner, Václav Veverka, PavlÃna ÅezáÄová,