The small GTPase Rap1 induces integrin activation via an inside-out signaling pathway mediated by the Rapl-interacting adaptor mol- ecule （RIAM）. Blocking this pathway may suppress tumor metastasis and other disease...The small GTPase Rap1 induces integrin activation via an inside-out signaling pathway mediated by the Rapl-interacting adaptor mol- ecule （RIAM）. Blocking this pathway may suppress tumor metastasis and other diseases that are related to hyperactive integrins. However, the molecular basis for the specific recognition of RIAM by Rap1 remains largely unknown. Herein we present the crystal structure of an active, GTP-bound GTPase domain of Rap1 in complex with the Ras association （RA）-pleckstrin homology （PH） structural module of RIAM at 1.65 A. The structure reveals that the recognition of RIAM by Rap1 is governed by side-chain interactions. Several side chains are critical in determining specificity of this recognition, particularly the Lys31 residue in Rap1 that is oppositely charged compared with the Glu31/Asp31 residue in other Ras GTPases. Lys31 forms a salt bridge with RIAM residue Glu212, making it the key specificity determinant of the interaction. We also show that disruption of these interactions results in reduction of Rapl：RIAM association, leadingto a loss of co-clustering and cell adhesion. Our findings elucidate the molecular mechanism by which RIAM med- iates Rapl-induced integrin activation. The crystal structure also offers new insight into the structural basis for the specific recruitment of RA-PH module-containing effector proteins by their smaU GTPase partners.展开更多
Deposition of clean and defect-free atomically thin two-dimensional crystalline flakes on surfaces by mechanical exfoliation of layered bulk materials has proven to be a powerful technique, but it requires a fast, rel...Deposition of clean and defect-free atomically thin two-dimensional crystalline flakes on surfaces by mechanical exfoliation of layered bulk materials has proven to be a powerful technique, but it requires a fast, reliable and non-destructive way to identify the atomically thin flakes among a crowd of thick flakes. In this work, we provide general guidelines to identify ultrathin flakes of TaSe2 by means of optical microscopy and Raman spectroscopy. Additionally, we determine the optimal substrates to facilitate the optical identification of atomically thin TaSe2 crystals. Experimental realization and isolation of ultrathin layers of TaSe2 enables future studies on the role of the dimensionality in interesting phenomena such as superconductivity and charge density waves.展开更多
文摘The small GTPase Rap1 induces integrin activation via an inside-out signaling pathway mediated by the Rapl-interacting adaptor mol- ecule （RIAM）. Blocking this pathway may suppress tumor metastasis and other diseases that are related to hyperactive integrins. However, the molecular basis for the specific recognition of RIAM by Rap1 remains largely unknown. Herein we present the crystal structure of an active, GTP-bound GTPase domain of Rap1 in complex with the Ras association （RA）-pleckstrin homology （PH） structural module of RIAM at 1.65 A. The structure reveals that the recognition of RIAM by Rap1 is governed by side-chain interactions. Several side chains are critical in determining specificity of this recognition, particularly the Lys31 residue in Rap1 that is oppositely charged compared with the Glu31/Asp31 residue in other Ras GTPases. Lys31 forms a salt bridge with RIAM residue Glu212, making it the key specificity determinant of the interaction. We also show that disruption of these interactions results in reduction of Rapl：RIAM association, leadingto a loss of co-clustering and cell adhesion. Our findings elucidate the molecular mechanism by which RIAM med- iates Rapl-induced integrin activation. The crystal structure also offers new insight into the structural basis for the specific recruitment of RA-PH module-containing effector proteins by their smaU GTPase partners.
文摘Deposition of clean and defect-free atomically thin two-dimensional crystalline flakes on surfaces by mechanical exfoliation of layered bulk materials has proven to be a powerful technique, but it requires a fast, reliable and non-destructive way to identify the atomically thin flakes among a crowd of thick flakes. In this work, we provide general guidelines to identify ultrathin flakes of TaSe2 by means of optical microscopy and Raman spectroscopy. Additionally, we determine the optimal substrates to facilitate the optical identification of atomically thin TaSe2 crystals. Experimental realization and isolation of ultrathin layers of TaSe2 enables future studies on the role of the dimensionality in interesting phenomena such as superconductivity and charge density waves.
