Intrasteric Inhibition Mediates the Interaction of the I/LWEQ Module Proteins Talin1, Talin2, Hip1, and Hip12 with Actin

详细信息    查看全文

• 作者：Melissa A. Senetar ; Stanley J. Foster ; and Richard O. McCann
• 刊名：Biochemistry
• 出版年：2004
• 出版时间：December 14, 2004
• 年：2004
• 卷：43
• 期：49
• 页码：15418 - 15428
• 全文大小：456K
• 年卷期：v.43,no.49(December 14, 2004)
• ISSN：1520-4995

文摘

The I/LWEQ module superfamily is a class of actin-binding proteins that contains a conservedC-terminal actin-binding element known as the I/LWEQ module. I/LWEQ module proteins include themetazoan talins, the cellular slime mold talin homologues TalA and TalB, fungal Sla2p, and the metazoanSla2 homologues Hip1 and Hip12 (Hip1R). These proteins possess a similar modular organization thatincludes an I/LWEQ module at their C-termini and either a FERM domain or an ENTH domain at theirN-termini. As a result of this modular organization, I/LWEQ module proteins may serve as linkers betweencellular compartments, such as the plasma membrane and the endocytic machinery, and the actincytoskeleton. Previous studies have shown that I/LWEQ module proteins bind to F-actin. In this report,we have determined the affinity of the I/LWEQ module proteins Talin1, Talin2, huntingtin interactingprotein-1 (Hip1), and the Hip1-related protein (Hip1R/Hip12) for F-actin and identified a conservedstructural element that interferes with the actin binding capacity of these proteins. Our data support thehypothesis that the actin-binding determinants in native talin and other I/LWEQ module proteins arecryptic and indicate that the actin binding capacities of Talin1, Talin2, Hip1, and Hip12 are regulated byintrasteric occlusion of primary actin-binding determinants within the I/LWEQ module. We have alsofound that the I/LWEQ module contains a dimerization motif and stabilizes actin filaments againstdepolymerization. This activity may contribute to the function of talin in cell adhesion and the roles ofHip1, Hip12 (Hip1R), and Sla2p in endocytosis.