کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2029895 | 1070989 | 2010 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Two-State Conformations in the Hyaluronan-Binding Domain Regulate CD44 Adhesiveness under Flow Condition Two-State Conformations in the Hyaluronan-Binding Domain Regulate CD44 Adhesiveness under Flow Condition](/preview/png/2029895.png)
SummaryThe hyaluronan (HA) receptor CD44 mediates cell adhesion in leukocyte trafficking and tumor metastasis. Our previous nuclear magnetic resonance (NMR) studies revealed that the CD44 hyaluronan-binding domain (HABD) alters its conformation upon HA binding, from the ordered (O) to the partially disordered (PD) conformation. Here, we demonstrate that the HABD undergoes an equilibrium between the O and PD conformations, in either the presence or absence of HA, which explains the seemingly contradictory X-ray and NMR structures of the HA-bound HABD. An HABD mutant that exclusively adopts the PD conformation displayed a higher HA affinity than the wild-type. Rolling of the cells expressing the mutant CD44 was less efficient than those expressing the wild-type, due to the decreased tether frequency and the slow cellular off rate. Considering that the mutant CD44, devoid of the low-affinity state, exhibited impaired rolling, we conclude that the coexistence of the high- and low-affinity states of the HABD is essential for the CD44-mediated rolling.
Graphical AbstractFigure optionsDownload high-quality image (135 K)Download as PowerPoint slideHighlights
► CD44 HABD exists in two-state equilibrium either in the ligand-free or bound states
► Ligand-binding shifts the equilibrium from the O form to the PD form
► O and PD form represents low- and high-affinity states for ligand, respectively
► Two-state equilibrium is crucial for CD44-mediated cell rolling under flow condition
Journal: - Volume 18, Issue 5, 12 May 2010, Pages 649–656