The crystal structure of protein-transporting chaperone BCP1 from Saccharomyces cerevisiae

Lin, Meng-Hsuan; Kuo, Po-Chih; Chiu, Yi‐Chih; Chang, Yi‐Chung; Chen, Sheng-Chia; Hsu, Chun‐Hua

doi:10.1016/j.jsb.2020.107605

Cited by 5 publications

(8 citation statements)

References 39 publications

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“…S2A). Strikingly, the structure showed that BCCIPα adopts a structural fold that is completely different from the structure of BCCIPβ published previously (see details below) ( 34 , 35 ). Analyses of this structure allowed us to design a new construct, BCCIPα-ΔL, containing a larger deletion (residues 231 to 280) of a long disordered loop (fig.…”

Section: Resultscontrasting

confidence: 81%

“…The previously published structures of BCCIPβ from human and yeast both exhibit a fold similar to GCN-5-related acetyltransferases, characterized by a splayed seven-stranded β sheet that is surrounded by several α helices on each side (Fig. 4A) (34,35). BCCIPβ is, however, unlikely an acetyltransferase because it lacks the catalytic residues conserved in those enzymes (34,35).…”

Section: Unique Fold Of Bccipαmentioning

confidence: 83%

“…4A ) ( 34 , 35 ). BCCIPβ is, however, unlikely an acetyltransferase because it lacks the catalytic residues conserved in those enzymes ( 34 , 35 ). BCCIPα also contains a central β sheet, but the order and directions of the β strands are entirely different from those in BCCIPβ ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, models of BCCIPα generated by AlphaFold without using structural templates and ESMFold that uses language model-based prediction closely resemble the structure of BCCIPβ, rather than that of BCCIPα solved here (fig. S4) (34)(35)(36)(37)(38). Furthermore, A DALI search of the protein structural database suggested that the fold of BCCIPα is unique, as the search failed to find any protein with substantial similarity to BCCIPα.…”

Section: Unique Fold Of Bccipαmentioning

confidence: 99%

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Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold

et al. 2023

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The FAM46 (also known as TENT5) proteins are noncanonical poly(A) polymerases (PAPs) implicated in regulating RNA stability. The regulatory mechanisms of FAM46 are poorly understood. Here, we report that the nuclear protein BCCIPα, but not the alternatively spliced isoform BCCIPβ, binds FAM46 and inhibits their PAP activity. Unexpectedly, our structures of the FAM46A/BCCIPα and FAM46C/BCCIPα complexes show that, despite sharing most of the sequence and differing only at the C-terminal portion, BCCIPα adopts a unique structure completely different from BCCIPβ. The distinct C-terminal segment of BCCIPα supports the adoption of the unique fold but does not directly interact with FAM46. The β sheets in BCCIPα and FAM46 pack side by side to form an extended β sheet. A helix-loop-helix segment in BCCIPα inserts into the active site cleft of FAM46, thereby inhibiting the PAP activity. Our results together show that the unique fold of BCCIPα underlies its interaction with and functional regulation of FAM46.

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Section: Resultscontrasting

confidence: 81%

Section: Unique Fold Of Bccipαmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Unique Fold Of Bccipαmentioning

confidence: 99%

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Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold

et al. 2023

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“…Whether BCCIP is an enzyme, and what its substrates might be are unclear. While we were engaged in trying to figure out its structure–function relationship, a yeast BCP1 structure was reported (with the structure coordinates on hold) 13 . Here we present crystal structures of the conserved isoform of human BCCIPβ and its outstanding binding surfaces for partner proteins and possibly for small molecules.…”

Section: Introductionmentioning

confidence: 99%

Structure of human BCCIP and implications for binding and modification of partner proteins

et al. 2021

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BCCIP was isolated based on its interactions with tumor suppressors BRCA2 and p21. Knockdown or knockout of BCCIP causes embryonic lethality in mice. BCCIP deficient cells exhibit impaired cell proliferation and chromosome instability. BCCIP also plays a key role in biogenesis of ribosome 60S subunits. BCCIP is conserved from yeast to humans, but it has no discernible sequence similarity to proteins of known structures. Here we report two crystal structures of an N‐terminal truncated human BCCIPβ, consisting of residues 61–314. Structurally BCCIP is similar to GCN5‐related acetyltransferases (GNATs) but contains different sequence motifs. Moreover, both acetyl‐CoA and substrate‐binding grooves are altered in BCCIP. A large 19‐residue flap over the putative CoA binding site adopts either an open or closed conformation in BCCIP. The substrate binding groove is significantly reduced in size and is positively charged despite the acidic isoelectric point of BCCIP. BCCIP has potential binding sites for partner proteins and may have enzymatic activity.

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Dual protection by Bcp1 and Rkm1 ensures incorporation of uL14 into pre-60S ribosomal subunits

Yeh,

Hsu,

Chu

et al. 2024

Journal of Cell Biology

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Eukaryotic ribosomal proteins contain extended regions essential for translation coordination. Dedicated chaperones stabilize the associated ribosomal proteins. We identified Bcp1 as the chaperone of uL14 in Saccharomyces cerevisiae. Rkm1, the lysine methyltransferase of uL14, forms a ternary complex with Bcp1 and uL14 to protect uL14. Rkm1 is transported with uL14 by importins to the nucleus, and Bcp1 disassembles Rkm1 and importin from uL14 simultaneously in a RanGTP-independent manner. Molecular docking, guided by crosslinking mass spectrometry and validated by a low-resolution cryo-EM map, reveals the correlation between Bcp1, Rkm1, and uL14, demonstrating the protection model. In addition, the ternary complex also serves as a surveillance point, whereas incorrect uL14 is retained on Rkm1 and prevented from loading to the pre-60S ribosomal subunits. This study reveals the molecular mechanism of how uL14 is protected and quality checked by serial steps to ensure its safe delivery from the cytoplasm until its incorporation into the 60S ribosomal subunit.

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The crystal structure of protein-transporting chaperone BCP1 from Saccharomyces cerevisiae

Cited by 5 publications

References 39 publications

Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold

Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold

Structure of human BCCIP and implications for binding and modification of partner proteins

Dual protection by Bcp1 and Rkm1 ensures incorporation of uL14 into pre-60S ribosomal subunits

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