Proteins Binding to the Carbohydrate HNK-1: Common Origins?

TY - JOUR

T1 - Proteins Binding to the Carbohydrate HNK-1: Common Origins?

AU - Castillo, Gaston

AU - Kleene, Ralf

AU - Schachner, Melitta

AU - Loers, Gabriele

AU - Torda, Andrew E

PY - 2021/7/29

Y1 - 2021/7/29

N2 - The human natural killer (HNK-1) carbohydrate plays important roles during nervous system development, regeneration after trauma and synaptic plasticity. Four proteins have been identified as receptors for HNK-1: the laminin adhesion molecule, high-mobility group box 1 and 2 (also called amphoterin) and cadherin 2 (also called N-cadherin). Because of HNK-1's importance, we asked whether additional receptors for HNK-1 exist and whether the four identified proteins share any similarity in their primary structures. A set of 40,000 sequences homologous to the known HNK-1 receptors was selected and used for large-scale sequence alignments and motif searches. Although there are conserved regions and highly conserved sites within each of these protein families, there was no sequence similarity or conserved sequence motifs found to be shared by all families. Since HNK-1 receptors have not been compared regarding binding constants and since it is not known whether the sulfated or non-sulfated part of HKN-1 represents the structurally crucial ligand, the receptors are more heterogeneous in primary structure than anticipated, possibly involving different receptor or ligand regions. We thus conclude that the primary protein structure may not be the sole determinant for a bona fide HNK-1 receptor, rendering receptor structure more complex than originally assumed.

AB - The human natural killer (HNK-1) carbohydrate plays important roles during nervous system development, regeneration after trauma and synaptic plasticity. Four proteins have been identified as receptors for HNK-1: the laminin adhesion molecule, high-mobility group box 1 and 2 (also called amphoterin) and cadherin 2 (also called N-cadherin). Because of HNK-1's importance, we asked whether additional receptors for HNK-1 exist and whether the four identified proteins share any similarity in their primary structures. A set of 40,000 sequences homologous to the known HNK-1 receptors was selected and used for large-scale sequence alignments and motif searches. Although there are conserved regions and highly conserved sites within each of these protein families, there was no sequence similarity or conserved sequence motifs found to be shared by all families. Since HNK-1 receptors have not been compared regarding binding constants and since it is not known whether the sulfated or non-sulfated part of HKN-1 represents the structurally crucial ligand, the receptors are more heterogeneous in primary structure than anticipated, possibly involving different receptor or ligand regions. We thus conclude that the primary protein structure may not be the sole determinant for a bona fide HNK-1 receptor, rendering receptor structure more complex than originally assumed.

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - CD57 Antigens/chemistry

KW - Cadherins/chemistry

KW - HMGB1 Protein/chemistry

KW - HMGB2 Protein/chemistry

KW - Humans

KW - Laminin/chemistry

KW - Ligands

KW - Nerve Regeneration/physiology

KW - Neuronal Plasticity/physiology

KW - Oligosaccharides/chemistry

KW - Protein Binding

KW - Protein Domains

U2 - 10.3390/ijms22158116

DO - 10.3390/ijms22158116

M3 - SCORING: Journal article

C2 - 34360882

VL - 22

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 15

M1 - 8116

ER -