title: Cocrystal structure of the ICAP1 PTB domain in complex with a KRIT1 peptide.
abstract: Integrin cytoplasmic domain-associated protein-1 (ICAP1) is a suppressor of integrin activation and directly binds to the cytoplasmic tail of β1 integrins; its binding suppresses integrin activation by competition with talin. Krev/Rap1 interaction trapped-1 (KRIT1) releases ICAP1 suppression of integrin activation by sequestering ICAP1 away from integrin cytoplasmic tails. Here, the cocrystal structure of the PTB domain of ICAP1 in complex with a 29-amino-acid fragment (residues 170-198) of KRIT1 is presented to 1.7 Å resolution [the resolution at which 〈I/σ(I)〉 = 2.9 was 1.83 Å]. In previous studies, the structure of ICAP1 with integrin β1 was determined to 3.0 Å resolution and that of ICAP1 with the N-terminal portion of KRIT1 (residues 1-198) was determined to 2.54 Å resolution; therefore, this study provides the highest resolution structure yet of ICAP1 and allows further detailed analysis of the interaction of ICAP1 with its minimal binding region in KRIT1.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. liuweizhi@ouc.edu.cn
authors.forename: Weizhi
authors.initials: W
authors.lastname: Liu
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D003460:Crystallization; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D000075927:KRIT1 Protein; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108257:ITGB1BP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins
keywords: ICAP1; KRIT1; PTB domain