Limits...
LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function.

Rothballer A, Schwartz TU, Kutay U - Nucleus (2013)

Bottom Line: The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM).Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling.They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.

ABSTRACT
Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM). In the lumen of the NE, the SUN and KASH domains engage in an intimate assembly to jointly form a NE bridge. Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling. They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

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Figure 3. The SUN-KASH complex. LINC complexes are hexamers. Three KASH peptides (yellow, orange, green) bind to the subunit interfaces of a SUN domain trimer (shades of blue), where they are tightly anchored by the binding pocket and the KASH lid of the SUN domain. Presentations were generated for the human SUN2/KASH2 complex (PDB 4XDS).
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Figure 3: Figure 3. The SUN-KASH complex. LINC complexes are hexamers. Three KASH peptides (yellow, orange, green) bind to the subunit interfaces of a SUN domain trimer (shades of blue), where they are tightly anchored by the binding pocket and the KASH lid of the SUN domain. Presentations were generated for the human SUN2/KASH2 complex (PDB 4XDS).

Mentions: The first crystal structures of a SUN domain protein, human SUN2, therefore bore some surprise: SUN2 is a trimer (Fig. 3).8,9 The shape of the complex resembles a lollipop, with the three SUN domains forming a globular head, from which the N-terminal extensions of the domains emanate as a helical stalk. The stalk folds into an unusual, right-handed, trimeric coiled coil. A conserved salt bridge between the stalk and the SUN domains holds the two elements in a rigid orientation and may serve to organize the spatial arrangement of the globular head. In fact, the trimeric organization of SUN2 is the essential prerequisite for the assembly of LINC complexes. Isolated SUN domains lacking their helical extensions are monomeric in solution and are deficient in recruiting KASH domain proteins both in vitro and in vivo.8


LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function.

Rothballer A, Schwartz TU, Kutay U - Nucleus (2013)

Figure 3. The SUN-KASH complex. LINC complexes are hexamers. Three KASH peptides (yellow, orange, green) bind to the subunit interfaces of a SUN domain trimer (shades of blue), where they are tightly anchored by the binding pocket and the KASH lid of the SUN domain. Presentations were generated for the human SUN2/KASH2 complex (PDB 4XDS).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585024&req=5

Figure 3: Figure 3. The SUN-KASH complex. LINC complexes are hexamers. Three KASH peptides (yellow, orange, green) bind to the subunit interfaces of a SUN domain trimer (shades of blue), where they are tightly anchored by the binding pocket and the KASH lid of the SUN domain. Presentations were generated for the human SUN2/KASH2 complex (PDB 4XDS).
Mentions: The first crystal structures of a SUN domain protein, human SUN2, therefore bore some surprise: SUN2 is a trimer (Fig. 3).8,9 The shape of the complex resembles a lollipop, with the three SUN domains forming a globular head, from which the N-terminal extensions of the domains emanate as a helical stalk. The stalk folds into an unusual, right-handed, trimeric coiled coil. A conserved salt bridge between the stalk and the SUN domains holds the two elements in a rigid orientation and may serve to organize the spatial arrangement of the globular head. In fact, the trimeric organization of SUN2 is the essential prerequisite for the assembly of LINC complexes. Isolated SUN domains lacking their helical extensions are monomeric in solution and are deficient in recruiting KASH domain proteins both in vitro and in vivo.8

Bottom Line: The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM).Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling.They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.

ABSTRACT
Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM). In the lumen of the NE, the SUN and KASH domains engage in an intimate assembly to jointly form a NE bridge. Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling. They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

Show MeSH