Structural Aspects of NF-B and IkB Proteins - Transcription Factors NF-kappaB - page 9

activation of transcription. In this chapter, we review the current state of NF- κ B

molecular biology from the perspective of protein structure and biochemistry.

2.2. THE NF- κ B PROTEINS

B family consists of five closely related polypeptide
subunits that associate to form transcriptionally active homo- and heterodimers
(Figure 2.1a). Each of the subunits shares high sequence homology within a con-
served Rel Homology Domain (RHD), a stretch of ~300 residues near the amino-
terminus. Contained within the RHD of NF-

The entire mammalian NF- κ

κ B subunits are all of the amino acid

(a)

NF- κ B

Class I

RHD

p50
p52

433

NTD DimD L G

G NTD DimD L 447

Class II

p65

NTD DimD L TA D 551

c-Rel
RelB

NTD DimD L TA D 619

557

LZ NTD DimD L TA D

(b)

I κ B

Canonical I B

κ

I κ B α 317

K S E ANK ANK ANK ANK ANK AN PEST

I κ B β 356

K S ANK ANK ANK ANK ANK ANK PEST

I κ B ε 361

K S ANK ANK ANK ANK ANK ANK

NF- κ B precursors

p105 NTD DimD L G 969

ANK ANK ANK ANK ANK ANK ANK DeaD S

p100 NTD DimD L G 898

ANK ANK ANK ANK ANK ANK ANK DeaD S

Nuclear I κ B

Bcl-3 446

ANK ANK ANK ANK ANK ANK ANK

I κ B ζ 629

ANK ANK ANK ANK ANK ANK ANK

B
polypeptides are divided into classes I and II based on the absence or presence of a carboxyl-
terminal transcriptional activation domain (TAD). Other abbreviations are RHD — Rel homol-
ogy region; NTD — Amino-terminal domain; DimD — Dimerization domain; L — Nuclear
localization sequence; G — Glycine-rich region; LZ — Leucine zipper. The number of amino
acids in the full-length human primary sequence is indicated on the right. (b) I

FIGURE 2.1 Domain organization of the mammalian NF- κ B and I κ B proteins. (a) NF- κ

κ B proteins

are categorized into canonical, NF- B precursors, and nuclear, as in the text. Additional

abbreviations used are ANK — Ankyrin repeat; K — Lysine site for signal-dependent ubiq-
uitinylation; S — Serine site of signal-dependent phosphorylation; PEST — region rich in
the amino acids proline, glutamic acid, serine, and threonine; DeaD — Death domain.

κ