Interactions and cooperativity between P-glycoprotein structural domains determined by thermal unfolding provides insights into its solution structure and function

详细信息    查看全文

• 作者：Zhengrong Yang^a ; Qingxian Zhou^a ; Leo Mok^b ; Anukriti Singh^b ; Douglas J. Swartz^b ; Ina L. Urbatsch^b ; ^{ina.urbatsch@ttuhsc.edu} ; Christie G. Brouillette^a ; ^c ; ^{christie@uab.edu}
• 关键词：AMPPCP ; β ; γ-methylene ATP ; CD ; circular dichroism ; CU ; cooperative unit ; CFTR ; cystic fibrosis transmembrane conductance regulator ; DDM ; n-dodecyl-β-d-maltopyranoside ; ΔHc ; calorimetric enthalpy ; DLS ; dynamic light scattering ; DMNG ; decyl maltose neopentyl glycol ; DSC ; differential scanning calorimetry ; ΔTm ; shift in thermal unfolding temperature ; His6&ndash ; Smt3 ; hexahistidine-SUMO protein tag ; ICL ; intracellular loop ; IMP ; integral membrane protein ; LS ; light scattering ; LUV ; large unilamella
• 刊名：Biochimica et Biophysica Acta (BBA) - Biomembranes
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：1859
• 期：1
• 页码：48-60
• 全文大小：1411 K
• 卷排序：1859

文摘

P-glycoprotein thermal unfolding data indicate two cooperative unfolding units. Each cooperative unit contains one NBD and two contacting intracellular loops. P-glycoprotein is predominantly inward-facing under continuous ATP hydrolysis. Outward-facing conformation in wild-type P-glycoprotein is transient. Outward-facing conformation is detected by DSC only when ATP hydrolysis is disabled.