EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII

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	EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII
	ZHENG CHUNLEI ; LIU HUIHUI ; Zhou JH(周佳海) ; ZHANG BIN
刊名	Blood
	2010
卷号	115 期号:5 页码:1081-1087
ISSN号	0006-4971
其他题名	EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII
英文摘要	Combined deficiency of factor V and factor VIII (F5F8D) is a bleeding disorder caused by mutations in either LMAN1 or MCFD2. LMAN1 (ERGIC-53) and MCFD2 form a Ca2+-dependent cargo receptor that cycles between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment for efficient transport of FV/FVIII from the ER to the Golgi. Here we show that the C-terminal EF-hand domains are both necessary and sufficient for MCFD2 to interact with LMAN1. MCFD2 with a deletion of the entire N-terminal non-EF hand region still retains the LMAN1-binding function. Deletions that disrupt core structure of the EF-hand domains abolish LMAN1 binding. Circular dichroism spectroscopy studies on missense mutations localized to different structural elements of the EF-hand domains suggest that Ca2+-induced folding is important for LMAN1 interaction. The EF-hand domains also mediate the interaction with FV and FVIII. However, mutations in MCFD2 that disrupt the tertiary structure and abolish LMAN1 binding still retain the FV/FVIII binding activities, suggesting that this interaction is independent of Ca2+-induced folding of the protein. Our results suggest that the EF-hand domains of MCFD2 contain separate binding sites for LMAN1 and FV/FVIII that are essential for cargo receptor formation and cargo loading in the ER. (Blood. 2010;115:1081-1087)
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1182/blood-2009-09-241877
语种	英语
WOS记录号	WOS:000274287500022
公开日期	2013-08-21
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/27801]
专题	上海有机化学研究所_上海有机化学研究所
推荐引用方式 GB/T 7714	ZHENG CHUNLEI,LIU HUIHUI,Zhou JH,et al. EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII[J]. Blood,2010,115(5):1081-1087.
APA	ZHENG CHUNLEI,LIU HUIHUI,周佳海,&ZHANG BIN.(2010).EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII.Blood,115(5),1081-1087.
MLA	ZHENG CHUNLEI,et al."EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII".Blood 115.5(2010):1081-1087.