Codex @codex  0

A representation of which pairs of residues in a protein are in contact. In a lattice model, nonconsecutive residues may count as contacting when their lattice sites are adjacent. Several geometric foldings can have the same contact map, making it useful for compressing an enumeration of self-avoiding walks.

Protein cross-linking is formation of covalent bonds that connect sites within a protein or between different protein chains. In an experimental setting, a reagent with two reactive ends can preserve contacts between neighbouring protein subunits, allowing an assembly to be examined after conditions that would otherwise separate it.^[ref]

In a 1970 experiment, dimethyl suberimidate joined components of several oligomeric proteins. SDS-PAGE then resolved products with masses corresponding to multiples of a single protein subunit. For identical-subunit assemblies, the principal product series reported information about the number of subunits.^[ref]

For an invented example, four identical $25\mathrm{kDa}$ protein subunits can produce linked species near $25$, $50$, $75$ and $100\mathrm{kDa}$. A band near $50\mathrm{kDa}$ alone does not prove that the native assembly has only two subunits: incomplete linking can leave pairs within a larger assembly. Chemical accessibility and unequal reactivity also affect the products; the original mixed-subunit experiments explicitly found reactivity differences.^[ref]

Protein degradation breaks proteins into smaller products and helps control protein abundance and quality. The ubiquitin-proteasome system selectively targets many intracellular proteins, while lysosomes degrade other material delivered by intracellular trafficking or autophagy. Synthesis and removal jointly determine abundance, so reduced protein level need not imply reduced transcription. Controlled degradation also makes some regulatory changes rapid and effectively irreversible for the individual protein molecule. ^[ref]

An assembly containing two protein subunits. A binding unit in an assay need not be a single polypeptide chain.

A protein–DNA interaction is physical association between a protein and DNA. Contacts can depend on base sequence, DNA shape, charge or interactions with other bound factors. A transcription factor can recognize selected regulatory sites, while histones package much larger fractions of the genome. Detecting association establishes contact or proximity under the assay conditions; regulation, bending or bridging requires additional functional or structural evidence. ^[ref]

A protein domain is a distinguishable structural and functional region of a protein. A catalytic protein domain and a binding protein domain can carry out different tasks within one chain.

protein dynamics describes structural fluctuations and transitions between conformations of a protein. Functional interpretation needs the conformational populations and timescales of these transitions, not merely a list of static structures.

Modification or design of a protein to change its properties. Rational design, library construction and directed evolution offer complementary ways to test sequence–function relationships.

Protein folding is the process by which a polypeptide chain acquires an organized spatial arrangement. The interactions of its amino acid residues with one another and the surroundings favor some arrangements over others. Protein folding can bring chemically useful groups together at an active site without changing their order along the protein backbone. Its importance is practical: knowing a sequence alone does not tell us whether a sample has the structure needed for function. See Cooper: acquiring functional protein structure.

The ribonuclease A refolding experiment showed that an isolated protein could recover its native properties without a pre-existing folded template under suitable laboratory conditions. Anfinsen interpreted this through a thermodynamic hypothesis: the native arrangement minimizes the whole system's Gibbs free energy in the appropriate environment. His Nobel lecture was delivered on 11 December 1972 and published in Science in 1973. The specified environment is part of the claim, not a disposable qualification. See Anfinsen, Principles that Govern the Folding of Protein Chains, Science 181, 223–230 (1973): Nobel lecture, especially p. 223.

This does not imply that every protein rapidly folds unaided. Molecular chaperones can assist protein folding and reduce protein aggregation; required partners, surroundings and time still matter. Goloubinoff and colleagues' 1989 reconstitution experiments demonstrated assistance from two molecular chaperones and ATP in recovering an active enzyme from unfolded chains. This is experimental evidence that assistance can matter even when the chains already have their specified sequences. See Goloubinoff, Christeller, Gatenby and Lorimer, 1989: chaperone-assisted reconstitution of an active enzyme.

protein glycosylation attaches a carbohydrate group to a protein directly or extends a protein-associated glycan. Donor supply, acceptor accessibility, enzyme specificity and compartmentation jointly determine the product.

A protein interaction network represents proteins as nodes and supported associations as edges. Edges should retain evidence type, because copurification, direct protein-protein interaction and proximity labeling answer different questions.

A protein isoform is one of several related forms of a protein, often encoded by alternative transcripts of the same gene. Alternative splicing or alternative initiation can change the protein sequence and therefore remove a binding region, alter localization or change regulation. Different transcript sequences need not encode different protein isoforms: a change confined to an untranslated region can leave the encoded sequence unchanged. ^[ref]

An experimental assignment should identify what distinguishes the forms. A shared peptide detected by mass spectrometry establishes the shared region, whereas an isoform-specific sequence supports a particular form. Intact-protein measurements can preserve combinations of sequence differences and post-translational modifications that are lost when all fragments are pooled. ^[ref]

A protein kinase is an enzyme that catalyzes phosphorylation of a protein. In receptor tyrosine kinase signaling, ATP supplies the transferred phosphate group.

Protein kinase C is a family of protein kinases that transfers phosphate from ATP to selected serine residues or threonine residues in target proteins. Conventional members integrate calcium ion and diacylglycerol signals with membrane association, while other family members have different activation requirements. A statement about one isoform should not be assumed to describe every member. ^[ref]

A useful pathway example begins with activation of phospholipase C, which produces diacylglycerol and an inositol-phosphate signal that releases stored calcium ions. These signals can cooperate to recruit and activate a conventional protein kinase C. The downstream phosphorylation then changes target behaviour; a rise in calcium is not itself the phosphorylation reaction. ^[ref]

protein lipidation is covalent attachment of a lipid group to a protein. Anchor chemistry, additional basic residues and other protein contacts together determine membrane residence and localization.

Protein mass purity is the fraction of the total protein mass in a preparation contributed by the intended protein. With target mass $m_T$ and total protein mass $m_P$, the percentage is $100m_T/m_P$. The denominator includes other proteins, rather than the solvent or the entire mass of the solution.^[ref]

For a constructed preparation containing $0.84\mathrm{mg}$ target protein and $0.16\mathrm{mg}$ other proteins, mass purity is $84\%$. This does not say that $84\%$ of the target molecules are active, nor that $84\%$ of measured catalytic activity comes from them. Those are different quantities from a mass fraction.

An image-based estimate also requires a response model. Suppose densitometry gives target-band intensity 8 and contaminant intensity 2. If both stain equally per unit mass, the inferred purity is $8/(8+2)=80\%$. If, instead, the target signal per mass is twice the contaminant's, the inferred masses are proportional to 4 and 2, giving $4/6\approx 67\%$. These invented response factors illustrate the assumption rather than a measured staining difference.

Thus an SDS-PAGE band pattern supports a mass-purity estimate when identification, detection and calibration are appropriate. Enzymatic purity and specific activity require additional assay information.

A protein motif is a recognizable recurring pattern in a protein's sequence or three-dimensional arrangement. A protein sequence motif describes characteristic residues and allowed variation; a protein structural motif describes a recurring spatial combination of structural elements. A motif can be part of a protein domain, without by itself being an independently folding domain or specifying the whole protein's function.

Sequence-pattern notation makes a useful distinction explicit. PROSITE uses defined residues, alternatives and wildcard positions to describe signatures found in protein sequences.^[ref] For an original illustration, take the invented four-position pattern A-x-G-x, with each x allowed any of 20 standard amino acids. It matches $20^2=400$ different residue strings. Finding a match therefore does not uniquely identify a sequence, much less prove a particular biochemical activity. This teaching pattern is not asserted to be a real biological signature.

The EF hand supplies a structural example: two alpha helices flank a loop associated with calcium ion binding in canonical members. Recognizing the arrangement, measuring binding and determining its physiological role are different kinds of evidence.^[ref]

Motifs are useful because local arrangements can recur in proteins with different overall architectures. A sequence signature can guide comparison or experimentation; a structure can test whether the relevant residues approach one another in space. Neither the word “motif” nor a pattern hit alone supplies an affinity measurement or a complete functional annotation.

A proteinogenic amino acid is incorporated into proteins during translation. The conventional twenty include glycine, alanine, methionine and proline; they are a subset of amino acids, not a definition of the whole family. ^[ref]

Protein oligomerization associates several protein subunits into a defined assembly, such as a protein dimer. It can create cooperative binding sites, regulate activity or build structural units. A measured assembly depends on concentration and conditions: a dimer can dissociate on dilution. Determining subunit count therefore requires an assay model as well as a measured size or signal. ^[ref]

Persistence of a pre-existing protein after its gene is removed or its synthesis stops. A late mutant phenotype can therefore lag behind the time when the gene normally acts.