ColabFold - Making protein folding accessible to all

Mirdita, Milot; Schütze, Konstantin; Moriwaki, Yoshitaka; Heo, Lim; Овчинников, С. Г.; Steinegger, Martin

doi:10.21203/rs.3.rs-1032816/v1

Cited by 404 publications

(643 citation statements)

References 4 publications

(5 reference statements)

Supporting

Mentioning

618

Contrasting

Unclassified

Order By: Relevance

“…On the corresponding surface of SiaQM there is also a cluster of conserved residues (around Q L1-2, M L5b-6, M L7-8). d , Complex of the SiaQM cryo-EM structure and SiaP crystal structure based on the binding mode predicted by AlphaFold2 39 . An interaction hotspot (inset, right) shows a number of titratable residues at the interface.…”

Section: Resultsmentioning

confidence: 99%

Structure and mechanism of the tripartite ATP-independent periplasmic (TRAP) transporter

Davies

Currie

North

et al. 2022

Preprint

View full text Add to dashboard Cite

In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential carboxylate- and sulfonate-containing nutrients into the cytoplasm. Unlike other secondary active transporters, TRAP transporters cannot receive their substrates directly, but do so indirectly via a secreted soluble substrate-binding protein. How a sodium-driven secondary active transporter is strictly coupled to a passenger-carrying substrate-binding domain is poorly understood. Here, we report the cryo-EM structure of the sialic acid TRAP transporter SiaQM from Photobacterium profundum at 2.97 A resolution. SiaM has 12-TMs that come together to form a transport domain and a scaffold domain, with the transport domain consisting of helical hairpins as seen in the sodium-coupled elevator transporter VcINDY. Interestingly, the SiaQ protein forms intimate contacts with SiaM to extend the size of the scaffold domain, indicating TRAP transporters may operate as monomers, rather than the typically observed oligomers. We have identified the Na+ and sialic acid binding sites in SiaM and confirmed a strict dependence on the substrate-binding protein SiaP for uptake. We have determined the SiaP crystal structure that, together with co-evolution driven docking studies, provides a molecular basis for how sialic acid is delivered to the SiaQM transporter complex. We conclude that TRAP proteins are conceptually a marriage between an ABC importer and a secondary active transporter, which we describe herein as an elevator-with-an-operator mechanism.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure and mechanism of the tripartite ATP-independent periplasmic (TRAP) transporter

Davies

Currie

North

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This inability of KabC to catalyze cyclization on the longer cNGG and NGG substrates represents a marked difference between the DA isomer–forming RadC and DabC versus the KA-forming KabC. While no obvious single residue can be attributed to these differences in substrate specificity, structural prediction via AlphaFold2 ( 34 , 35 ) reveals KabC enzyme models to have an extended loop that pushes further into the active site than in RadC or DabC models ( Fig. 3 B ).…”

Section: Resultsmentioning

confidence: 98%

Domoic acid biosynthesis in the red alga Chondria armata suggests a complex evolutionary history for toxin production

Steele

Brunson

Maeno

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Originally isolated from the red alga Chondria armata , domoic acid (DA) is best known as a potent marine neurotoxin produced by oceanic harmful algal blooms of planktonic diatoms. Sequencing efforts to date of kainoid-producing red algae have focused exclusively on a closely related molecule, kainic acid, leaving a gap in the understanding of DA biosynthesis in red algae and its evolutionary linkage to diatoms. Here, we present the phylogenetic and biochemical investigation of DA biosynthesis in C. armata . This work demonstrates the high synteny of DA biosynthetic genes between relatively distant taxonomic groups of algae and suggests a complex evolutionary history for DA biosynthesis involving gene transfer and neofunctionalization.

show abstract

“…A consequence, suggested by this study, is that many V-set and I-set Ig domains go undetected in non-bilaterians and other understudied taxa. As genomes continue to be sequenced, our ability to detect these domains has been enhanced by new methods for detecting remote homologs and producing highly accurate structural models (Jumper et al, 2021; Mirdita et al, 2021; Tunyasuvunakool et al, 2021). These new data will undoubtedly enhance our understanding of how Ig domains evolved and may force us to revisit how these families are defined.…”

Section: Discussionmentioning

confidence: 99%

“…For single domain predictions, we generated a custom multiple sequence alignment which was submitted, along with the query sequence, to Colabfold via the “AlphaFold2_mmseqs2” notebook, version 1.1 (Mirdita et al, 2021). The input multiple sequence alignment was generated as follows.…”

Section: Methodsmentioning

confidence: 99%

A family of unusual immunoglobulin superfamily genes in an invertebrate histocompatibility complex

Huene

Sanders

et al. 2022

Preprint

View full text Add to dashboard Cite

Invertebrate histocompatibility—also known as allorecognition—has long interested marine ecologists, population geneticists, evolutionary biologists, and immunologists, but its genetic basis remains enigmatic in most species. Here, we report the nearly complete sequence of a histocompatibility complex from the colonial cnidarian, Hydractinia symbiolongicarpus. This sequence reveals that the two known Hydractinia allorecognition genes, Allorecognition 1 (Alr1) and Allorecognition 2 (Alr2) are part of a large family of immunoglobulin superfamily (IgSF) genes, several of which are candidates for new allodeterminants. These genes encode transmembrane proteins with domain architectures similar to cell-adhesion molecules and immune receptors. Several also contain cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) and immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Our data, which include highly accurate protein structure predictions, reveal that these proteins have V-set and I-set domains with unusual sequence signatures. This suggests the last common ancestor of cnidarians and bilaterians had distinct V-set and I-set Ig domains.

show abstract

ColabFold - Making protein folding accessible to all

Cited by 404 publications

References 4 publications

Structure and mechanism of the tripartite ATP-independent periplasmic (TRAP) transporter

Structure and mechanism of the tripartite ATP-independent periplasmic (TRAP) transporter

Domoic acid biosynthesis in the red alga Chondria armata suggests a complex evolutionary history for toxin production

A family of unusual immunoglobulin superfamily genes in an invertebrate histocompatibility complex

Contact Info

Product

Resources

About