Identifying nature's protein lego set

Das, Sudeshna; Smith, Temple F.

doi:10.1016/s0065-3233(00)54006-6

Cited by 31 publications

(25 citation statements)

References 36 publications

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“…Concatenated and nested domains are commonly observed but overlapping (interlaced) protein domains are rare49. Interlaced domains have an alternating arrangement of SSEs of two folds along a single polypeptide.…”

Section: Resultsmentioning

confidence: 99%

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

Kaur

Subramanian

2016

Sci Rep

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Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.

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Section: Resultsmentioning

confidence: 99%

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

Kaur

Subramanian

2016

Sci Rep

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“…The analogy between modular protein domains and Lego blocks, which implicitly stipulates reiterated and combinatorial use of domains by Nature to create repertoires of functional complexes [6,55], is an attractive, widely accepted concept. Only recently did I learn the origin of the name Lego -the word is an abbreviated fusion of two Danish words 'leg godt', meaning 'have fun playing'.…”

Section: Discussionmentioning

confidence: 99%

The WW Domain

Sudol

2004

Modular Protein Domains

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“…The prevalence of proteins with more than two domains and the recurrent appearance of the same domain in non-homologues proteins show that functional domains are reused when creating new proteins. Because of this, domains have been likened to Lego bricks that can be recombined in various ways to build proteins with completely new functions [5]. Hence, one way to study evolution of protein function and structure is by looking at the evolution of protein domain composition.…”

Section: Introductionmentioning

confidence: 99%

The evolution of protein domain families

Buljan

Bateman

2009

Biochemical Society Transactions

113

100

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Protein domains are the common currency of protein structure and function. Over 10 000 such protein families have now been collected in the Pfam database. Using these data along with animal gene phylogenies from TreeFam allowed us to investigate the gain and loss of protein domains. Most gains and losses of domains occur at protein termini. We show that the nature of changes is similar after speciation or duplication events. However, changes in domain architecture happen at a higher frequency after gene duplication. We suggest that the bias towards protein termini is largely because insertion and deletion of domains at most positions in a protein are likely to disrupt the structure of existing domains. We can also use Pfam to trace the evolution of specific families. For example, the immunoglobulin superfamily can be traced over 500 million years during its expansion into one of the largest families in the human genome. It can be shown that this protein family has its origins in basic animals such as the poriferan sponges where it is found in cell-surface-receptor proteins. We can trace how the structure and sequence of this family diverged during vertebrate evolution into constant and variable domains that are found in the antibodies of our immune system as well as in neural and muscle proteins.

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Identifying nature's protein lego set

Cited by 31 publications

References 36 publications

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

The WW Domain

The evolution of protein domain families

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