CoRNeA: A pipeline to decrypt the inter protein interfaces from amino acid sequence information

Chopra, Kriti; Burdak, Bhawna; Sharma, Kaushal; Kembhavi, Ajit; Mande, Shekhar C.; Chauhan, Radha

doi:10.1101/741280

Cited by 3 publications

(6 citation statements)

References 53 publications

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“…Earlier, we developed a computational tool, CoRNeA (Co-evolution Random forest and Network Analysis), which can predict binary interacting interfaces solely based on the primary protein sequences (Chopra et al 2020). We employed this tool to predict precise interacting regions among Nup88, Nup214 and Nup62.…”

Section: Resultsmentioning

confidence: 99%

“…We employed this tool to predict precise interacting regions among Nup88, Nup214 and Nup62. A concatenated multiple sequence alignment file (only structured regions) of two interacting partners namely: Nup62•Nup88, Nup88•Nup214 and Nup214•Nup62 were used in the CoRNeA workflow as described previously (Chopra et al 2020). The final interface outputs were sorted based on convolution scores as high scoring residue pairs indicating a very high probability of these residue pairs to form the interactive interface between the two proteins (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Co-evolution Random forest and Network analysis was performed using primary amino acid sequences from both the proteins in a complex as the input information as described in Chopra et al 2020. Only the structured regions of Nup88 (1-742), Nup62 (320-525) and Nup214 (1-1100) were considered for the predictions.…”

Section: Methodsmentioning

confidence: 99%

“…The cross-linking mass spectrometry data suggests the inter-domain interaction network between the subunits of Nup82 complex and with the linker Nups (such as Nup98, Nup145C and Nup145N) that are responsible for the NPC assembly ( As Nup88•Nup62•Nup214 complex is central to the CR, we explored the detailed interaction studies followed by biochemical reconstitution of this mammalian complex to understand the role of individual Nups. To characterise the interaction networks, we performed the in-silico protein-protein interactions prediction using CoRNeA platform (Chopra et al 2020) coupled with in-vitro tandem affinity pull down (TAP) assays and dissected the inter-domain interactions among these three Nups. Our study revealed that the α-helical coiled-coil regions of these proteins are critical to form stable complexes of Nup88•Nup62 and Nup88•Nup62•Nup214.…”

Section: Introductionmentioning

confidence: 99%

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Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex

Madheshiya

Shukla

Singh

et al. 2022

Preprint

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The nuclear pore complex (NPC) is a highly modular assembly of 34 distinct nucleoporins (Nups), to form a versatile transport channel between the nucleus and cytoplasm. Among them, Nup62 is known as an essential component for nuclear transport while, Nup93 for the proper nuclear envelope assembly. These Nups constitute various NPC subcomplexes: such as central transport channel (CTC), cytoplasmic ring (CR) and inner ring (IR). However, how they play their role in the NPC assembly and transport activity is not clear. Here we delineated the interacting regions, conducted biochemical reconstitution and structural characterization of the mammalian CR complex to reveal its intrinsic dynamic behaviour and a distinct 4 shaped architecture resembling the CTC complex. Our data demonstrate that Nup62 coiled-coil domain is critical to forming both Nup62-Nup88 and Nup62-Nup88-Nup214 heterotrimers and both can bind to the Nup93. We therefore propose that Nup93 act as a sensor to bind to Nup62 shared heterotrimers including Nup62-Nup54 heterotrimer of the CTC, which was not shown previously as an interacting partner. Altogether, our study establishes that the Nup62 via its coiled-coil domain is central to form compositionally distinct yet structurally similar heterotrimers, and the Nup93 anchors these diverse heterotrimers by recognizing them non-selectively.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex

Madheshiya

Shukla

Singh

et al. 2022

Preprint

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“…Further, it revealed human Nup155 has vertebrate-specific insertions and deletions that provide distinct features to its β-propeller domain. We deciphered precise Nup155 interacting sites with Nup93 and Nup35 using CoRNeA(Chopra et al, 2020). Based on these interactions and structural analysis, we show that vertebrate-specific unique insertions in the 1-112 region of Nup155 are critical for Nup35 and Nup93 interaction and located in the vicinity of AF-linked genetic mutation site (R391).…”

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confidence: 99%

Cryo-EM structure of human Nup155 reveals the biochemical basis for atrial fibrillation linked genetic mutation R391H

Niranjan

Singh

Chauhan

2021

Preprint

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Human nuclear pore complexes are composed of ≈32 distinct nucleoporins to facilitate bidirectional nucleo-cytoplasmic transport. Many of them have been associated with various human diseases such as an inherited mutation (R391H) in Nup155 is shown as the clinical cause of atrial fibrillation and sudden cardiac arrest. Due to the lack of structural knowledge and mechanistic insights, the roles of Nups in NPC assembly and relevance in human diseases are very restricted. Here, we show the cryo-EM structure of human Nup155 at 5.2-5.7 Å resolution deciphered from 3 distinct particle classes: N-terminus (19-863), C-terminus (864-1337), and longer N-terminus (19-1069). It revealed intrinsic plasticity at the middle domain of Nup155 and the role of species-specific loop regions in an atypical 7-bladed β-propeller domain to provide a distinct interface for Nup93 and Nup35. Due to the proximity of these Nups interacting sites near the Arginine-391 position, atrial fibrillation linked genetic mutation (R391H) causes dissociation from NPC in absence of N-terminal 112 residues

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Workshop on RanBP2/Nup358 and acute necrotizing encephalopathy

Palazzo

Joseph

Lim

et al. 2022

Nucleus

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Dominant missense mutations in RanBP2/Nup358 cause Acute Necrotizing Encephalopathy (ANE), a pediatric disease where seemingly healthy individuals develop a cytokine storm that is restricted to the central nervous system in response to viral infection. Untreated, this condition leads to seizures, coma, long-term neurological damage and a high rate of mortality. The exact mechanism by which RanBP2 mutations contribute to the development of ANE remains elusive. In November 2021, a number of clinicians and basic scientists presented their work on this disease and on the interactions between RanBP2/Nup358, viral infections, the innate immune response and other cellular processes.

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CoRNeA: A pipeline to decrypt the inter protein interfaces from amino acid sequence information

Cited by 3 publications

References 53 publications

Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex

Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex

Cryo-EM structure of human Nup155 reveals the biochemical basis for atrial fibrillation linked genetic mutation R391H

Workshop on RanBP2/Nup358 and acute necrotizing encephalopathy

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