STRUCTURE AND FUNCTION OF

DIFFERENT NUCLEAR PROTEINS

BY AKSHAT TEWARI (1073)

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The nucleoplasm contains many types of complex proteins. The nuclear proteins can be categorized into following two
types :
◦ (i) Basic proteins. The proteins which take basic stain are known as the basic proteins. The most important basic
proteins of the nucleus are nucleoprotamines and the nucleohistones.
◦ The nucleoprotamines are simple and basic proteins having very low molecular weight (about 4000 daltons). The
most abundant amino acid of these proteins is arginine (pH 10 to 11). The protamines usually remain bounded with
the DNA molecules by the salt linkage. The protamines occur in the spermatozoa of the certain fishes.
◦ The nucleohistones have high molecular weight, e.g., 10,000 to 18,000 daltons. The histones are composed of basic
amino acids such as arginine, lysine and histidine. The histone proteins remain associated with the DNA by the ionic
bonds and they occur in the nuclei of most organisms.
◦ According to the composition of the amino acids following types of histone proteins have been recognised, e.g.,
histones rich in lysine, histones with arginine and histones with poor amount of the lysine.
◦ (ii) Non-histone or Acidic -The acidic proteins either occur in the nucleoplasm or in the chromatin. The most abundant
acidic proteins of the euchromatin (a type of chromatin) are the phosphoproteins
◦ 3. Enzymes. The nucleoplasm contains many enzymes which are necessary for the synthesis of the DNA and RNA.
Most of the nuclear enzymes are composed of non-histone (acidic) proteins. The most important nuclear enzymes are
the DNA polymerase, RNA polymerase
Histone Proteins
◦ The orderly packaging of eukaryotic DNA depends on histones, a remarkable group of small proteins that possess an
unusually high content of the basic amino acids arginine and lysine.
◦ Histones are divided into five classes( H1, H2A, H2B, H3 ,H4) which can be distinguished by their arginine/lysine ratio.
◦ The amino acid sequences of histones, particularly H3 and H4, have undergone very little change over long periods of
evolutionary time.(One reason is histones interact with the backbone of the DNA molecule, which is identical in all
organisms.)
◦ DNA and histones are organized into repeating subunits, called nucleosomes
◦ Each nucleosome contains a nucleosome core particle consisting of 146 base
. pairs of supercoiled DNA wrapped almost twice around a disk-shaped
complex of eight histone molecules.
◦ The histone core of each nucleosome consists of two copies each of histones
H2A, H2B, H3, and H4 assembled into an octamer, as discussed below. The
remaining histone—type H1—resides outside the nucleosome core particle.
The H1 histone is referred to as a linker histone because it binds to part of the
linker DNA that connects one nucleosome core particle to the next.
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◦ The eight histone molecules that comprise a nucleosome core particle are organized into four
heterodimers: two H2A-H2B dimers and two H3-H4 dimers
◦ Dimerization of histone molecules is mediated by their C-terminal domains, which consist
largely of helices (represented by the cylinders) folded into a compact mass in the core of the
nucleosome.
◦ In contrast, the N-terminal segment of each core histone (and also the C-terminal segment of
H2A) takes the form of a long, flexible tail , that extends past the DNA helix and into the
surroundings.
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◦ In addition to the four “conventional” core histones discussed above, several
alternate versions of the H2A and H3 histones are also synthesized in most
cells. The importance of these histone variants, as they are called, remains
largely unexplored, but they are thought to have specialized functions
NUCLEOPORINS
◦ Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex
(NPC).
◦ Nucleoporins, a family of around 30 proteins, are the main components of the nuclear pore complex in eukaryotic
cells
◦ Nucleoporins are able to transport molecules across the nuclear envelope at a very high rate. A single NPC is
able to transport 60,000 protein molecules across the nuclear envelope every minute.
 FUNCTION
◦ Nucleoporins regulate the transport of macromolecules through the nuclear envelope
via interactions with the transporter molecules karyopherins. Karyopherins will bind to
their cargo, and reversibly interact with the FG-repeats in nucleoporins. Karyopherins
and their cargo are passed between FG-repeats until they diffuse down their
concentration gradient and through the nuclear pore complex. Karyopherins can
serve as an importin (transporting proteins into the nucleus) or an exportin
(transporting proteins out of the nucleus).Karyopherins release of their cargo is
driven by Ran, a G protein. Ran is small enough that it can diffuse through nuclear
pores down its concentration gradient without interacting with nucleoporins. Ran will
bind to either GTP or GDP and has the ability to change a karyopherin's affinity for its
cargo. Inside the nucleus, RanGTP causes an importin karyopherin to change
conformation, allowing its cargo to be released. RanGTP can also bind to exportin
karyopherins and pass through the nuclear pore. Once it has reached the cytosol,
RanGTP can be hydrolyzed to RanGDP, allowing the exportin's cargo to be released
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Types of karyopherins and function
Lamins (makes up the nuclear lamina)
◦ Lamins, also known as nuclear lamins are fibrous proteins providing structural function and transcriptional
regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the
nuclear lamina on the interior of the nuclear envelope
◦ Mammalian cells have three lamin genes, designated A, B, and C, which code for at least seven distinct
proteins.
◦ Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during
mitosis, the positioning of nuclear pores, and programmed cell death.
◦ The structure of lamins is composed of three units that are common among intermediate
filaments: a central α-helical rod domain containing heptad repeats surrounded by globular N
and C-terminal domains.
◦ The N-terminal is shorter and located at the top (head) while the C-terminal is longer and
located at the end (tail)
◦ All C-terminal domains contain a nuclear localization sequence (NLS)
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LBR (LAMIN BINDING RECEPTOR)
◦ The protein localizes to the inner membrane of the nuclear envelope and anchors the lamina and the
heterochromatin to the membrane.

◦ EMERIN
protein composed of 254 amino acids. Emerin is a serine-rich
◦ Emerin is a 29.0 kDa
protein with an N-terminal 20-amino acid hydrophobic region that is flanked by
charged residues; the hydrophobic region may be important for anchoring the protein
to the membrane, with the charged terminal tails being cytosolic.
◦ It mediates membrane anchorage to the cytoskeleton.
◦ expression of emerin is highest in skeletal and cardiac muscle.
COILIN
◦ Coilin protein is one of the main molecular components of Cajal bodies. Cajal bodies are non-
membrane bound nuclear bodies of varying number and composition that are involved in the
post-transcriptional modification of small nuclear and small nucleolar RNAs.
◦ coilin acts as glue to connect the CB to the nucleolus. The N-terminus of the coilin protein
directs its self-oligomerization while the C-terminus influences the number of nuclear bodies
assembled per cell. Differential methylation and phosphorylation of coilin likely influences its
localization among nuclear bodies and the composition and assembly of Cajal bodies.

◦ PML
◦ Promyelocytic leukemia protein (PML) PML protein is a tumor suppressor
protein required for the assembly of a number of nuclear structures,
called PML-nuclear bodies, which form amongst the chromatin of the
cell nucleus.
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◦ The PML-NBs have a wide array of functions, and a large role in cell regulation The true
function, however, remains unclear, and several possible models have been proposed for PML-
NB function, including nuclear storage of proteins, serving as a dock where other proteins
accumulate to be post-translationally modified, direct involvement with transcription, and
chromatin regulation.
 Nucleoplasmin
◦ Nucleoplasmin, is a thermostable acidic protein.
◦ The pentameric protein participates in various significant cellular activities like sperm chromatin remodeling
, nucleosome assembly, genome stability, ribosome biogenesis, DNA duplication and
transcriptional regulation.
◦ Nucleoplasmin (NP) is made out of five monomers,that create ring-shaped histone chaperone. The
monomers are formed by a core domain that make the protein highly stable and compact.
◦ The NP core is made out of eight β strands that form a barrel with a jellyroll topology.
◦ During the assembly of regular nucleosomal arrays(A nucleosomal array consists of core histone octamer-
DNA complexes spaced at approximately 200 bp intervals along a DNA molecule. Nucleosomal arrays are
the fundamental building block of chromosomal superstructures, the substrate for transcription, and the first
nucleoprotein assembly laid down after DNA replication), these nucleoplasmins transfer the DNA to them by
binding to the histones. This reaction requires ATP.
◦ Nucleoplasmin has several acidic side chains that interact with the basic
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residues of histones, thereby reducing their high positive charge density
through transient electrostatic interactions and preventing the nonspecific
aggregation of histones with DNA
◦ These include a highly conserved N-terminal domain that contains a
small tract with four to twelve acidic residues (labeled A1)and a C-
terminal domain with larger acidic tracts.
◦ Two such tracts are present in the C-terminal domain of
Nucleoplasmin ( A2 and A3 ).
◦ A bipartite nuclear localization signal is also located between the A2
and A3 tracts in Np.
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